G-CSF动员MSCs对严重颅脑创伤小鼠的救治作用与机制研究
|
摘要
颅脑创伤是战时和平时常发生的严重伤类,救治尤其困难,伤亡和伤残率为严重创伤之首。据报道,全世界每年至少有1千万颅脑创伤病人。在美国,每年有1.4百万颅脑创伤病人,死亡达5万人。我国每年有百万以上的严重颅脑创伤病人,其中死亡约10万人,而存活伤员多并发伤残。可见,颅脑创伤已成为全球严重的公共卫生问题。如何降低死亡率、减少伤残率是创伤医学领域一直攻克的难题,取得了一些进展,特别是通过多种手段综合救治,在一定程度上减轻或控制全身性损害的发生发展,降低了死亡率。但对促进脑组织再生修复、神经功能恢复尚未取得突破性进展,主要原因是神经细胞再生极为困难。
以往认为神经元细胞是终末分化的功能细胞,失去增殖能力。脑组织或脊髓组织损伤后的修复,主要由神经胶质细胞增殖修复,缺乏相应神经元再生,这种不完全性再生导致神经功能丧失,形成智残或肢残的严重后果。随着干细胞研究的不断深入,从脑组织中分离出神经干细胞,体外培养有增殖活性,并可向神经元细胞诱导分化,说明神经组织中存在少量具增殖活性的干细胞,可以通过体内途径增强其增殖并诱导向神经元细胞分化,可能有利于损伤组织的结构修复和功能康复。也可以利用神经干细胞具有体外增殖能力的特性,在体外将少量神经干细胞扩增并定向诱导后移植到损伤部位,或静脉移植随血液循环到达损伤部位促进其修复。但在临床应用中则难以实施,因为不可能从自体取材分离神经干细胞,获得异体神经干细胞亦十分困难,胚胎干细胞涉及伦理学问题,加之异体细胞移植的免疫排斥问题、体外扩增后的细胞成瘤风险等问题远未解决。
然而,成体干细胞具多向分化潜能的理论认识,为再生医学、创伤医学等研究领域开创了新局面,拓展了新思路,奠定了新途径。不少文献报道,骨髓间充质干细胞(mesenchymal stem cells, MSCs)具有可获得性(自体或异体来源)、体外大量扩增性和体外诱导的多向分化性(成骨分化、成肌分化、成脂分化、成神经细胞分化等),本单位前期研究还证实,将绿色荧光蛋白(GFP)转基因小鼠骨髓细胞静脉移植给受10Gyγ线全身照射的同种小鼠(多脏器损伤模型),移植的GFP阳性骨髓细胞广泛存在于受体小肠、肝、脑、皮肤等多种组织脏器,通过形态学结合免疫组化分析,有的移植细胞已转化为小肠上皮细胞、肝细胞和神经元样细胞,又将原代神经元细胞培养上清液加入MSCs培养体系,发现MSCs可转化表达神经元细胞的分子标志。综合体内体外结果分析认为,MSCs通过血液循环定植于损伤局部,并受局部壁龛微环境因素和体液因素调节分化为局部功能细胞。而生理情况下,MSCs大量存在骨髓,循环血液中仅有少量,如果采取措施动员骨髓中的MSCs进入血液循环,使定植于损伤局部的MSCs数量增加,并在微环境因素调节下分化为功能细胞,必将有利于创伤(包括颅脑创伤)组织修复和功能恢复。利用干细胞的生物学特性,切入创伤救治研究,探索促进创伤组织修复的实用新途径并阐明相关机理,对揭示干细胞分化受微环境调控机制和推进临床创伤救治具有重要意义。
因此,本课题第一部分建立从大鼠、人等不同种属外周血分离培养MSCs的方法,以成纤维细胞集落形成单位(colony forming units-fibroblast,CFU-F)技术定量分析动物体内注射粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)后,是否增加外周血MSCs数量,以明确G-CSF的动员效应,进一步分析经动员进入外周血的MSCs是否保留骨髓MSCs的分子标志和多向分化潜能,尤其是阐明能否向神经元细胞分化,有无神经元细胞的电生理活动。第二部分自行改进制作颅脑撞击伤致伤装具,复制严重颅脑创伤小鼠模型(50g×30cm撞击力),设计3种G-CSF剂量分别注射给3组致伤小鼠,观测动物14天内的累积死亡率,参照Bederson等评分方法和Shapira等评分方法对致伤小鼠分别进行神经行为学评分和运动功能评分的动态观测,从整体水平评估G-CSF动员骨髓细胞参与严重颅脑创伤的救治作用。由于G-CSF不仅可以动员骨髓MSCs进入血液循环,也可动员造血干祖细胞或其它细胞进入血液循环,参与颅脑创伤修复主要是哪类细胞?创伤局部主要是什么因素吸引循环细胞定植?定植后的细胞在原位能否转化为神经细胞?这些问题还鲜未阐明。故设计第三部分实验,Western blot方法检测对MSCs具趋化作用的基质源性细胞因子-1(stromal-derived factor-1,SDF-1)表达量的变化,采用经典方法将GFP转基因骨髓细胞分为MSCs细胞、造血干祖细胞和其它细胞3类,分别移植给颅脑创伤小鼠,以确定参与颅脑创伤修复的细胞类型,用双标(GFP和NeuN等神经细胞标志分子)免疫组化鉴定移植细胞的转化类型,获如下主要结果与结论。
1.对不同种属进行外周血MSCs分离培养,成功率不同,其直接原因是生理条件下外周血中存在的MSCs量少导致的。在本实验条件下,我们可以稳定的直接分离培养出大鼠外周血的MSCs。
2.通过CFU-F分析,证实G-CSF可以有效对动员大鼠骨髓和外周血MSCs(接近4倍),动员的外周血MSCs特性鉴定实验显示:其形态上和骨髓MSCs一致;并阳性表达MSCs的标志分子:CD44、CD73、CD90和CD106,不表达造血系的标志分子:CD31和CD45;并具有成骨、成脂和成神经元的分化能力。证实其为真正的MSCs。
3.体外实验证实,动员的MSCs可以在β-巯基乙醇、神经元原代培养上清液和组合诱导剂(含生长因子和化学分子的鸡尾酒似的混合诱导剂)诱导下向神经元分化,表达神经元标志分子:NF、NSE和NeuN。在神经元原代培养上清液的诱导下,动员的MSCs还可出现功能上的改变:类似神经元的内向钠电流。
4.确定撞击小鼠头部的撞击力为50g×30cm,建立稳定的小鼠严重颅脑创伤模型,为下一步的实验提供研究平台。
5.通过在不同时相点观察创伤小鼠的神经行为学和运动功能的改变、累积死亡率及病理切片,发现注射G-CSF后,严重颅脑创伤小鼠在神经行为学和运动功能上有显著改善,累计死亡率显著降低,从整体水平上证实G-CSF对严重颅脑创伤小鼠具有救治效应。并证实在本实验条件下,G-CSF的最佳动员剂量为20μg/kg.d。
6.将GFP转基因C57BL/6小鼠骨髓细胞通过贴壁培养和磁珠分选分成3种细胞:MSCs、造血干细胞、其它类细胞,流式细胞仪检测证实分选效果比较好。将分选的细胞移植到严重颅脑创伤小鼠,结果表明:在大脑组织中未发现GFP标记的造血干细胞和其它类细胞的定植。GFP标记的MSCs移植颅脑创伤小鼠后5d、10d、15d和20d,均在大脑发现GFP阳性细胞的表达。证实骨髓细胞中是MSCs参与了小鼠严重颅脑创伤的修复。
7. Western blot检测撞击伤小鼠创位不同时相点的SDF-1的表达,结果显示,小鼠严重颅脑创伤后,创位脑组织的SDF-1高表达,显著高于正常脑组织的SDF-1。在撞击伤后7d,SDF-1的表达达到高峰。Western blot检测撞击伤小鼠伤后第7d不同组织SDF-1的表达,结果显示,小鼠严重颅脑创伤第7d后,创位脑组织的SDF-1高表达,显著高于其他组织的SDF-1。其他组织中心脏的SDF-1表达最低。证实小鼠脑部创伤后可高表达SDF-1分子,吸引、趋化动员的MSCs向脑损伤部位移行、定植。
8. NeuN为神经元的特异标志分子,在核上表达。因此,用NeuN为一抗进行荧光免疫组化,可观察到脑组织神经元的分布情况。以荧光双标免疫组化实验来观察GFP标记的MSCs在脑创位向神经元(表达特异标志分子NeuN)的分化。结果显示,第10d和20d的标本都可见同时表达NeuN分子和GFP分子的移植细胞,证实移植的GFP标记MSCs在脑创位向神经元分化,从而参与严重颅脑创伤的修复。
9.以荧光双标免疫组化实验观察MSCs在严重颅脑创伤小鼠的创位向神经胶质细胞的分化。激光共聚焦显微镜结果显示,第7d、12d和20d的标本都可见同时表达GFAP分子和GFP分子的移植细胞,表明移植的MSCs(GFP标记)还可通过在脑创位向神经胶质细胞分化而促进严重颅脑创伤的修复。
10.基于上述研究结果,我们提出,对严重颅脑创伤伤员,采用G-CSF可有效动员骨髓间充质干细胞进入血液循环,循环中的间充质干细胞受损伤部位高表达SDF-1的吸引趋化而定植,定植的间充质干细胞可在局部微环境因素诱导下转化为神经元细胞和神经胶质细胞参与损伤组织修复,尤其有利于功能恢复。此方法实用性强,有良好的临床应用前景。
Traumatic brain injury (TBI) is a kind of serious injury happened in war time and peace time. Its treatment remains a great challenge, and the casualty and disable rate is the highest among serious trauma. At least 10 million patients with TBI worldwide are serious enough to result in death or hospitalization annually. In the United States, an average of 1.4 million TBI occur each year, and 50,000 deaths. There are about 1 million TBI patients every year in our country, and 100,000 of them can not survive the injury, and the most survivals are disabled, causing big burden on individuals and society as well. How to decrease the death rate and disable rate is a long-lasting tough problem in traumatic medicine. There are some advancement in the manipulation of TBI patients recent years, especailly by the combination of different countermeasures, which can lessen or prevent the further systemic damage and lower the death rate. However, the progress on promoting the regeneration of encephal tissue and the recovery of nerve function because nerve cells are difficult in regeneration and the stem cells only are confined to certain areas in brain.
Neurons were considered previously a terminal differentiated functional cell, and loss of reproductive activity. Brain and spinal cord injury were repaired main by glial cell replacement, but not by neurons. This unsatisfied reapir would result in neural functional incapacity, and disable in intellegence or motion. Pliles of Studies have confirmed that neural stem cells can be isolated from brain tissue, amplified in vitro, and induced to differentiate into neurons. So it is possible for neural stem cells in brain tissue to differentiate into neuron in vivo and promote the histological construction repair and functional rehabilitation in injured tissue. After amplification and committed differentiation induction in vitro, neural stem cells can be transplanted into injury site to promote damage repair. In fact, it is almost impossible to get human neural stem cells for thraputic amplification and differntiation induction in vitro. The idea of adopting embryonic stem cells has evoked contradiction in ethics in addition to the technique problems such as allograft-caused immunologic rejection and the risk of neoplastic tramsformation during in vitro amplification. These remianed problems need to be solved before the application of stem cell transplantation in clinic.
However, the multippotential differentiation, the plasticity, of adult stem cells has laid the foundation for new strategy and methods in the research interest of regeneration medicine and traumatic medicine. Increasing studies have reported that mesenchymal stem cells (MSCs) posses the characteristics, such as easy acquirement, (autoallergic or variant), feasible amplification in vitro and multipotential differentiation (to differentiate into osteocytes, muscle cells, adipocytes and neural cells). In our previous study, bone marrow cells from green fluorescent protein(GFP) transgenic mice were transplanted intravenously into homogenic mice with total-body irradiation of 10 Gyγray, and GFP-positive cells were found in intestine, liver, brain, skin of the recipients, confirming that the transplanted cells have differentiated or de-differntiated into enterocytes, hepatic cells and neurons. We also demonstrated that MSCs treated by supernatants of primary neural cell cultures expressed markers of neurons. From above findings, we drew the conclusion that MSCs can be recruited to the injury site through blood circulation and indued by the microenvironment (niche and humoral factors) to differentiate into specific tissue cells. Under physiological condition, the quantity of circulating MSCs that derived from bone marrow is too small to show theraputic effect. It is possible to increase the amount of MSCs recruited to injury site if take measures to mobilize MSCs from bone marrow to peripheral blood, and subsequently promote trauma tissue (include TBI) repair and function recovery. To explore the new way for trauma tissue repair and its mechanism will reveal the differentiation mechanism of MSCs regulated by microenvironment and facilitate clinic trauma care.
In first part of this study, peripheral blood MSCs from rat and human were isolated and cultured. Colony forming units-fibroblastc (CFU-F) assay was performed to evaluate the mobilization effect on MSCs by granulocyte colony-stimulating factor (G-CSF). The morphology, differentiation potential, especially to neuron, and immunophenotype of PB-derived adherent cells were detected. In second part of this study, the experimental mouse model of serious TBI was established (impact force 50g in weight and 30cm in high of free fall). the effect of MSCs mobilized by G-CSF on the trauma recovery of different severities was evaluated by recording neuroethology scores (reference Bederson), motor function scores (reference Shapira) and the animal mortality rate. As G-CSF could not only mobilize bone marrow MSCs but also haemopoietic stem cell, which population of cells participate trauma repair need to be clearified. What was the main factor to attracte circulating cells to the injury site? Could the cells recruit to injury site of brain transform to neuron? So we designed third part study, the expression of SDF-1 was detected by Western blot, bone marrow cells of GFP mice were fractionated into MSCs, HSCs and non-MSCs/HSCs cells by adherent culture and magnetic bead cell sorting. The fractionated cells were transplanted into TBI mice to find out which cell population of cells participate in trauma repair. The differentiation/transdifferentiation of MSCs labeled by GFP in situ in trauma site were detected by double immunofluorescence. Main results and conlusion were as follow:
1. PB MSCs were isolated and cultureed successfully or unsuccessfully from different genus, it concerned with many factor, especially a small number of circulating MSCs in BP. Under our experiment condition, rat’s PB MSCs could been isolated and cultured steadily.
2. we confirmed that G-CSF mobilized BM-derived MSCs, especially PB-derived MSCs (almost 4-fold increase) by CFU-F assay. PB-derived adherent cells formed a homogeneous cell layer that closely resembled BM MSCs. These cells were positive for marker molecule of MSCs: CD44, CD73, CD90, and CD106, but were negative for marker molecule of systema haemale: CD31 and CD45. These cells could be induced to differentiate into bone, lipoids and nerve cells. PB-derived adherent cells were considered bona fide MSCs in light of their morphology, differentiation potential, and immunophenotype.
3. MSCs mobilized by G-CSF were induced to differentiate into neurons withβ-mercap- toethanol, supernatants of nerve cell cultures and con-antileptic (contain growth factor and chemical molecular), and express nerve cell markers NF, NSE, and NeuN. These MSCs could appear introvert sodium current after inducing with supernatants of nerve cell cultures.
4. The experiment mouse model of serious TBI was established (impact force: 50g×30cm). It provided a experiment platform for research.
5. By research neuroethology scores, motor function scores and pathological section, result confirmed that G-CSF could significantly promote injury repair of serious TBI mice, and the mortality rate of mice after trauma was significantly degraded. Under our experiment condition, neuroethology and motor function scores were determined at different phase point after G-CSF mobilization, it was confirmed that the optimization mobilization dose was 20μg/kg.d.
6. We fractionated bone marrow cells of GFP mice into MSCs, HSCs, and non-MSCs/HSCs cells by adherent culture and using magnetic beads, detect result by flow cytometer showed separation effect was good. Transplanted these cell types into trauma mice, We confirmed no HSCs or non-MSCs/HSCs cells labeled by GFP planted in injury sites, but MSCs labeled by GFP could plant in injury sites on 5d, 10d, 15d and 20d after trauma. Hence, MSCs mobilized by G-CSF promoted trauma repair.
7. The expression of SDF-1 was detected by Western blot at trauma sites on different phase point. Result confirmed the expression of SDF-1 at trauma sites was significantly higher than that of normal brain tissue, and the expression of SDF-1 approached peak after trauma on 7d. The expression of SDF-1 was detected by Western blot in different tissue on 7d. Result confirmed the expression of SDF-1 at trauma sites was significantly higher than that of other tissue, and the expression of SDF-1 was lowest in heart. It could result in MSCs migrated to and planted in trauma sites.
8. As the idio-marker molecule of neuron, NeuN is express on neuron nucleus. So we carried out fluorescence immunocytochemically, and got the disposition condition of neuron at brain tissue. MSCs labeled by GFP planted in trauma sites were found by double immunofluorescence to express the neuron marker NeuN on 10d and 20d. These findings confirmed that MSCs could directly differentiate into neurons at brain trauma sites to promot trauma repair.
9. MSCs labeled by GFP planted in trauma sites were found by double immuno- fluorescence to express the glial cell marker GFAP on 7d, 12d and 20d. These findings suggest that MSCs can directly differentiate into glial cell at brain trauma sites to promot trauma repair.
10. In view of above study, we considered G-CSF could mobilize TBI patients’MSCs from bone marrow to PB, SDF-1 high expressed at trauma sites could result in MSCs migrated to and planted in trauma sites, and planting MSCs could be induced by microenvironment factor to directly differentiate into neuron and glial cell for promot trauma repair, especial for functional recovery. This method is very practical, and has a favourable prospect for clinic application.
以往认为神经元细胞是终末分化的功能细胞,失去增殖能力。脑组织或脊髓组织损伤后的修复,主要由神经胶质细胞增殖修复,缺乏相应神经元再生,这种不完全性再生导致神经功能丧失,形成智残或肢残的严重后果。随着干细胞研究的不断深入,从脑组织中分离出神经干细胞,体外培养有增殖活性,并可向神经元细胞诱导分化,说明神经组织中存在少量具增殖活性的干细胞,可以通过体内途径增强其增殖并诱导向神经元细胞分化,可能有利于损伤组织的结构修复和功能康复。也可以利用神经干细胞具有体外增殖能力的特性,在体外将少量神经干细胞扩增并定向诱导后移植到损伤部位,或静脉移植随血液循环到达损伤部位促进其修复。但在临床应用中则难以实施,因为不可能从自体取材分离神经干细胞,获得异体神经干细胞亦十分困难,胚胎干细胞涉及伦理学问题,加之异体细胞移植的免疫排斥问题、体外扩增后的细胞成瘤风险等问题远未解决。
然而,成体干细胞具多向分化潜能的理论认识,为再生医学、创伤医学等研究领域开创了新局面,拓展了新思路,奠定了新途径。不少文献报道,骨髓间充质干细胞(mesenchymal stem cells, MSCs)具有可获得性(自体或异体来源)、体外大量扩增性和体外诱导的多向分化性(成骨分化、成肌分化、成脂分化、成神经细胞分化等),本单位前期研究还证实,将绿色荧光蛋白(GFP)转基因小鼠骨髓细胞静脉移植给受10Gyγ线全身照射的同种小鼠(多脏器损伤模型),移植的GFP阳性骨髓细胞广泛存在于受体小肠、肝、脑、皮肤等多种组织脏器,通过形态学结合免疫组化分析,有的移植细胞已转化为小肠上皮细胞、肝细胞和神经元样细胞,又将原代神经元细胞培养上清液加入MSCs培养体系,发现MSCs可转化表达神经元细胞的分子标志。综合体内体外结果分析认为,MSCs通过血液循环定植于损伤局部,并受局部壁龛微环境因素和体液因素调节分化为局部功能细胞。而生理情况下,MSCs大量存在骨髓,循环血液中仅有少量,如果采取措施动员骨髓中的MSCs进入血液循环,使定植于损伤局部的MSCs数量增加,并在微环境因素调节下分化为功能细胞,必将有利于创伤(包括颅脑创伤)组织修复和功能恢复。利用干细胞的生物学特性,切入创伤救治研究,探索促进创伤组织修复的实用新途径并阐明相关机理,对揭示干细胞分化受微环境调控机制和推进临床创伤救治具有重要意义。
因此,本课题第一部分建立从大鼠、人等不同种属外周血分离培养MSCs的方法,以成纤维细胞集落形成单位(colony forming units-fibroblast,CFU-F)技术定量分析动物体内注射粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)后,是否增加外周血MSCs数量,以明确G-CSF的动员效应,进一步分析经动员进入外周血的MSCs是否保留骨髓MSCs的分子标志和多向分化潜能,尤其是阐明能否向神经元细胞分化,有无神经元细胞的电生理活动。第二部分自行改进制作颅脑撞击伤致伤装具,复制严重颅脑创伤小鼠模型(50g×30cm撞击力),设计3种G-CSF剂量分别注射给3组致伤小鼠,观测动物14天内的累积死亡率,参照Bederson等评分方法和Shapira等评分方法对致伤小鼠分别进行神经行为学评分和运动功能评分的动态观测,从整体水平评估G-CSF动员骨髓细胞参与严重颅脑创伤的救治作用。由于G-CSF不仅可以动员骨髓MSCs进入血液循环,也可动员造血干祖细胞或其它细胞进入血液循环,参与颅脑创伤修复主要是哪类细胞?创伤局部主要是什么因素吸引循环细胞定植?定植后的细胞在原位能否转化为神经细胞?这些问题还鲜未阐明。故设计第三部分实验,Western blot方法检测对MSCs具趋化作用的基质源性细胞因子-1(stromal-derived factor-1,SDF-1)表达量的变化,采用经典方法将GFP转基因骨髓细胞分为MSCs细胞、造血干祖细胞和其它细胞3类,分别移植给颅脑创伤小鼠,以确定参与颅脑创伤修复的细胞类型,用双标(GFP和NeuN等神经细胞标志分子)免疫组化鉴定移植细胞的转化类型,获如下主要结果与结论。
1.对不同种属进行外周血MSCs分离培养,成功率不同,其直接原因是生理条件下外周血中存在的MSCs量少导致的。在本实验条件下,我们可以稳定的直接分离培养出大鼠外周血的MSCs。
2.通过CFU-F分析,证实G-CSF可以有效对动员大鼠骨髓和外周血MSCs(接近4倍),动员的外周血MSCs特性鉴定实验显示:其形态上和骨髓MSCs一致;并阳性表达MSCs的标志分子:CD44、CD73、CD90和CD106,不表达造血系的标志分子:CD31和CD45;并具有成骨、成脂和成神经元的分化能力。证实其为真正的MSCs。
3.体外实验证实,动员的MSCs可以在β-巯基乙醇、神经元原代培养上清液和组合诱导剂(含生长因子和化学分子的鸡尾酒似的混合诱导剂)诱导下向神经元分化,表达神经元标志分子:NF、NSE和NeuN。在神经元原代培养上清液的诱导下,动员的MSCs还可出现功能上的改变:类似神经元的内向钠电流。
4.确定撞击小鼠头部的撞击力为50g×30cm,建立稳定的小鼠严重颅脑创伤模型,为下一步的实验提供研究平台。
5.通过在不同时相点观察创伤小鼠的神经行为学和运动功能的改变、累积死亡率及病理切片,发现注射G-CSF后,严重颅脑创伤小鼠在神经行为学和运动功能上有显著改善,累计死亡率显著降低,从整体水平上证实G-CSF对严重颅脑创伤小鼠具有救治效应。并证实在本实验条件下,G-CSF的最佳动员剂量为20μg/kg.d。
6.将GFP转基因C57BL/6小鼠骨髓细胞通过贴壁培养和磁珠分选分成3种细胞:MSCs、造血干细胞、其它类细胞,流式细胞仪检测证实分选效果比较好。将分选的细胞移植到严重颅脑创伤小鼠,结果表明:在大脑组织中未发现GFP标记的造血干细胞和其它类细胞的定植。GFP标记的MSCs移植颅脑创伤小鼠后5d、10d、15d和20d,均在大脑发现GFP阳性细胞的表达。证实骨髓细胞中是MSCs参与了小鼠严重颅脑创伤的修复。
7. Western blot检测撞击伤小鼠创位不同时相点的SDF-1的表达,结果显示,小鼠严重颅脑创伤后,创位脑组织的SDF-1高表达,显著高于正常脑组织的SDF-1。在撞击伤后7d,SDF-1的表达达到高峰。Western blot检测撞击伤小鼠伤后第7d不同组织SDF-1的表达,结果显示,小鼠严重颅脑创伤第7d后,创位脑组织的SDF-1高表达,显著高于其他组织的SDF-1。其他组织中心脏的SDF-1表达最低。证实小鼠脑部创伤后可高表达SDF-1分子,吸引、趋化动员的MSCs向脑损伤部位移行、定植。
8. NeuN为神经元的特异标志分子,在核上表达。因此,用NeuN为一抗进行荧光免疫组化,可观察到脑组织神经元的分布情况。以荧光双标免疫组化实验来观察GFP标记的MSCs在脑创位向神经元(表达特异标志分子NeuN)的分化。结果显示,第10d和20d的标本都可见同时表达NeuN分子和GFP分子的移植细胞,证实移植的GFP标记MSCs在脑创位向神经元分化,从而参与严重颅脑创伤的修复。
9.以荧光双标免疫组化实验观察MSCs在严重颅脑创伤小鼠的创位向神经胶质细胞的分化。激光共聚焦显微镜结果显示,第7d、12d和20d的标本都可见同时表达GFAP分子和GFP分子的移植细胞,表明移植的MSCs(GFP标记)还可通过在脑创位向神经胶质细胞分化而促进严重颅脑创伤的修复。
10.基于上述研究结果,我们提出,对严重颅脑创伤伤员,采用G-CSF可有效动员骨髓间充质干细胞进入血液循环,循环中的间充质干细胞受损伤部位高表达SDF-1的吸引趋化而定植,定植的间充质干细胞可在局部微环境因素诱导下转化为神经元细胞和神经胶质细胞参与损伤组织修复,尤其有利于功能恢复。此方法实用性强,有良好的临床应用前景。
Traumatic brain injury (TBI) is a kind of serious injury happened in war time and peace time. Its treatment remains a great challenge, and the casualty and disable rate is the highest among serious trauma. At least 10 million patients with TBI worldwide are serious enough to result in death or hospitalization annually. In the United States, an average of 1.4 million TBI occur each year, and 50,000 deaths. There are about 1 million TBI patients every year in our country, and 100,000 of them can not survive the injury, and the most survivals are disabled, causing big burden on individuals and society as well. How to decrease the death rate and disable rate is a long-lasting tough problem in traumatic medicine. There are some advancement in the manipulation of TBI patients recent years, especailly by the combination of different countermeasures, which can lessen or prevent the further systemic damage and lower the death rate. However, the progress on promoting the regeneration of encephal tissue and the recovery of nerve function because nerve cells are difficult in regeneration and the stem cells only are confined to certain areas in brain.
Neurons were considered previously a terminal differentiated functional cell, and loss of reproductive activity. Brain and spinal cord injury were repaired main by glial cell replacement, but not by neurons. This unsatisfied reapir would result in neural functional incapacity, and disable in intellegence or motion. Pliles of Studies have confirmed that neural stem cells can be isolated from brain tissue, amplified in vitro, and induced to differentiate into neurons. So it is possible for neural stem cells in brain tissue to differentiate into neuron in vivo and promote the histological construction repair and functional rehabilitation in injured tissue. After amplification and committed differentiation induction in vitro, neural stem cells can be transplanted into injury site to promote damage repair. In fact, it is almost impossible to get human neural stem cells for thraputic amplification and differntiation induction in vitro. The idea of adopting embryonic stem cells has evoked contradiction in ethics in addition to the technique problems such as allograft-caused immunologic rejection and the risk of neoplastic tramsformation during in vitro amplification. These remianed problems need to be solved before the application of stem cell transplantation in clinic.
However, the multippotential differentiation, the plasticity, of adult stem cells has laid the foundation for new strategy and methods in the research interest of regeneration medicine and traumatic medicine. Increasing studies have reported that mesenchymal stem cells (MSCs) posses the characteristics, such as easy acquirement, (autoallergic or variant), feasible amplification in vitro and multipotential differentiation (to differentiate into osteocytes, muscle cells, adipocytes and neural cells). In our previous study, bone marrow cells from green fluorescent protein(GFP) transgenic mice were transplanted intravenously into homogenic mice with total-body irradiation of 10 Gyγray, and GFP-positive cells were found in intestine, liver, brain, skin of the recipients, confirming that the transplanted cells have differentiated or de-differntiated into enterocytes, hepatic cells and neurons. We also demonstrated that MSCs treated by supernatants of primary neural cell cultures expressed markers of neurons. From above findings, we drew the conclusion that MSCs can be recruited to the injury site through blood circulation and indued by the microenvironment (niche and humoral factors) to differentiate into specific tissue cells. Under physiological condition, the quantity of circulating MSCs that derived from bone marrow is too small to show theraputic effect. It is possible to increase the amount of MSCs recruited to injury site if take measures to mobilize MSCs from bone marrow to peripheral blood, and subsequently promote trauma tissue (include TBI) repair and function recovery. To explore the new way for trauma tissue repair and its mechanism will reveal the differentiation mechanism of MSCs regulated by microenvironment and facilitate clinic trauma care.
In first part of this study, peripheral blood MSCs from rat and human were isolated and cultured. Colony forming units-fibroblastc (CFU-F) assay was performed to evaluate the mobilization effect on MSCs by granulocyte colony-stimulating factor (G-CSF). The morphology, differentiation potential, especially to neuron, and immunophenotype of PB-derived adherent cells were detected. In second part of this study, the experimental mouse model of serious TBI was established (impact force 50g in weight and 30cm in high of free fall). the effect of MSCs mobilized by G-CSF on the trauma recovery of different severities was evaluated by recording neuroethology scores (reference Bederson), motor function scores (reference Shapira) and the animal mortality rate. As G-CSF could not only mobilize bone marrow MSCs but also haemopoietic stem cell, which population of cells participate trauma repair need to be clearified. What was the main factor to attracte circulating cells to the injury site? Could the cells recruit to injury site of brain transform to neuron? So we designed third part study, the expression of SDF-1 was detected by Western blot, bone marrow cells of GFP mice were fractionated into MSCs, HSCs and non-MSCs/HSCs cells by adherent culture and magnetic bead cell sorting. The fractionated cells were transplanted into TBI mice to find out which cell population of cells participate in trauma repair. The differentiation/transdifferentiation of MSCs labeled by GFP in situ in trauma site were detected by double immunofluorescence. Main results and conlusion were as follow:
1. PB MSCs were isolated and cultureed successfully or unsuccessfully from different genus, it concerned with many factor, especially a small number of circulating MSCs in BP. Under our experiment condition, rat’s PB MSCs could been isolated and cultured steadily.
2. we confirmed that G-CSF mobilized BM-derived MSCs, especially PB-derived MSCs (almost 4-fold increase) by CFU-F assay. PB-derived adherent cells formed a homogeneous cell layer that closely resembled BM MSCs. These cells were positive for marker molecule of MSCs: CD44, CD73, CD90, and CD106, but were negative for marker molecule of systema haemale: CD31 and CD45. These cells could be induced to differentiate into bone, lipoids and nerve cells. PB-derived adherent cells were considered bona fide MSCs in light of their morphology, differentiation potential, and immunophenotype.
3. MSCs mobilized by G-CSF were induced to differentiate into neurons withβ-mercap- toethanol, supernatants of nerve cell cultures and con-antileptic (contain growth factor and chemical molecular), and express nerve cell markers NF, NSE, and NeuN. These MSCs could appear introvert sodium current after inducing with supernatants of nerve cell cultures.
4. The experiment mouse model of serious TBI was established (impact force: 50g×30cm). It provided a experiment platform for research.
5. By research neuroethology scores, motor function scores and pathological section, result confirmed that G-CSF could significantly promote injury repair of serious TBI mice, and the mortality rate of mice after trauma was significantly degraded. Under our experiment condition, neuroethology and motor function scores were determined at different phase point after G-CSF mobilization, it was confirmed that the optimization mobilization dose was 20μg/kg.d.
6. We fractionated bone marrow cells of GFP mice into MSCs, HSCs, and non-MSCs/HSCs cells by adherent culture and using magnetic beads, detect result by flow cytometer showed separation effect was good. Transplanted these cell types into trauma mice, We confirmed no HSCs or non-MSCs/HSCs cells labeled by GFP planted in injury sites, but MSCs labeled by GFP could plant in injury sites on 5d, 10d, 15d and 20d after trauma. Hence, MSCs mobilized by G-CSF promoted trauma repair.
7. The expression of SDF-1 was detected by Western blot at trauma sites on different phase point. Result confirmed the expression of SDF-1 at trauma sites was significantly higher than that of normal brain tissue, and the expression of SDF-1 approached peak after trauma on 7d. The expression of SDF-1 was detected by Western blot in different tissue on 7d. Result confirmed the expression of SDF-1 at trauma sites was significantly higher than that of other tissue, and the expression of SDF-1 was lowest in heart. It could result in MSCs migrated to and planted in trauma sites.
8. As the idio-marker molecule of neuron, NeuN is express on neuron nucleus. So we carried out fluorescence immunocytochemically, and got the disposition condition of neuron at brain tissue. MSCs labeled by GFP planted in trauma sites were found by double immunofluorescence to express the neuron marker NeuN on 10d and 20d. These findings confirmed that MSCs could directly differentiate into neurons at brain trauma sites to promot trauma repair.
9. MSCs labeled by GFP planted in trauma sites were found by double immuno- fluorescence to express the glial cell marker GFAP on 7d, 12d and 20d. These findings suggest that MSCs can directly differentiate into glial cell at brain trauma sites to promot trauma repair.
10. In view of above study, we considered G-CSF could mobilize TBI patients’MSCs from bone marrow to PB, SDF-1 high expressed at trauma sites could result in MSCs migrated to and planted in trauma sites, and planting MSCs could be induced by microenvironment factor to directly differentiate into neuron and glial cell for promot trauma repair, especial for functional recovery. This method is very practical, and has a favourable prospect for clinic application.
引文
1. Fredriksson R, Zhang L, Bostr?m O, et al. Influence of impact speed on head and brain injury outcome in vulnerable road user impacts to the car hood. Stapp Car Crash J. 2007 Oct;51:155-67.
2. Beschorner R, Dietz K, Schauer N, et al. Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol Histopathol, 2007; 22(5): 515-26.
3. BauzáG, Lamorte WW, Burke PA, et al. High mortality in elderly drivers is associated with distinct injury patterns: analysis of 187,869 injured drivers. J Trauma. 2008 Feb; 64(2):304-10.
4.郑文贵,李向云. 1996～2003年全国交通事故伤害的时间序列分析.中国卫生事业管理,2006; 2:105-7.
5. Baker AJ, Park E, Hare GM, et al. Effects of resuscitation fluid on neurologic physiology after cerebral trauma and hemorrhage. J Trauma. 2008 Feb;64(2):348-57.
6. Kraus MF, Susmaras T, Caughlin BP, et al. White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain. 2007 Oct;130(Pt 10):2508-19.
7. Williams A, Piaton G, Aigrot MS, et al. Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain. 2007 Oct;130(Pt 10):2554-65.
8. Mandel SA, Sagi Y, Amit T. Rasagiline promotes regeneration of substantia nigra dopaminergic neurons in post-MPTP-induced Parkinsonism via activation of tyrosine kinase receptor signaling pathway. Neurochem Res. 2007 Oct;32(10):1694-9.
9. Holmberg E, Nordstrom T, Gross M, et al. Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules found in central nervous system injury. J Neurotrauma. 2006 Sep;23(9):1366-78.
10. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
11. Ke Y, Chi L, Xu R, et al. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells. 2006; 24(4): 1011-1019..
12. McLaren A. A scientist's view of the ethics of human embryonic stem cell research. Cell Stem Cell. 2007 Jun 7;1(1):23-6.
13. Ando T, Yujiri T, Nomiyama J, et al. Allogeneic peripheral blood stem cell transplantation from related donors mismatched at 2 HLA loci in the host-versus-graft direction. Tohoku J Exp Med. 2008 Feb;214(2):159-63.
14. Zhang SJ, Zhang H, Hou M, et alIs it possible to obtain "true endothelial progenitor cells" by in vitro culture of bone marrow mononuclear cells? Stem Cells Dev. 2007 Aug;16(4):683-90.
15. Mouiseddine M, Fran?ois S, Semont A, et al. Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol. 2007 Sep;80 Spec No 1:S49-55.
16. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
17. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
18. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Zhonghua Yi Xue Za Zhi. 2005 Jul 20; 85(27): 1883-1884.
19. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb;25(2):371-379
20. Lee MW, Choi J, Yang MS, et al. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2004; 320: 273-278.
21. Bauhofer A, Schwarting RK, K?ster M, et al. Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials. Inflamm Res. 2004 Dec;53(12):697-705.
22. Zhang Y, Adachi Y, Suzuki Y, et al. Synergistic effects of granulocyte-colony stimulating factor and macrophage-colony stimulating factor on recovery of donor hematopoietic cells in allogeneic bone marrow transplantation. Oncol Rep. 2006Aug;16(2):367-71.
23. Chen J, Larochelle A, Fricker S, Bridger G, Dunbar CE, Abkowitz JL. Mobilization as a preparative regimen for hematopoietic stem cell transplantation. Blood. 2006; 107(9): 3764-3771.
24. Robinson SN, Pisarev VM, Chavez JM, et al . Use of matrix metalloproteinase (MMP)-9 knockout mice demonstrates that MMP-9 activity is not absolutely required for G-CSF or Flt-3 ligand-induced hematopoietic progenitor cell mobilization or engraftment. Stem Cells. 2003; 21(4): 417-427.
25. Zvaifler NJ, Marinova-ML, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000; 2: 477-488.
26. Lazarus HM, Haynesworth SE, Gerson SL, et al. Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother. 1997; 6: 447-455.
27. Burt RK, Loh Y, Pearce W, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA. 2008 Feb 27;299(8): 925-36.
28. Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008 Feb 22;132(4):681-96.
29. Chan BP, Hui TY, Yeung CW, et al. Self-assembled collagen-human mesenchymal stem cell microspheres for regenerative medicine. Biomaterials. 2007; 28(31): 4652-4666.
30. Guo CA, Liu XG, Huo JZ, et al. Novel gene-modified-tissue engineering of cartilage using stable transforming growth factor-beta1-transfected mesenchymal stem cells grown on chitosan scaffolds. J Biosci Bioeng. 2007; 103(6): 547-556.
31. Tiina M, Jarmo L. Placenta—an alternative source of stem cells . Toxicology and Applied Pharmacology 2005; 207( 2): 544-549.
32. Porada CD, Zanjani ED, Almeida-Porad G. Adult mesenchymal stem cells: a pluripotent population with multiple applications. Curr Stem Cell Res Ther. 2006 Sep;1(3):365-9.
33. Pountos I, Corscadden D, Emery P, et al. Mesenchymal stem cell tissue engineering: techniques for isolation, expansion and application. Injury. 2007 Sep;38 Suppl4:S23-33.
34. David CC,Reiner C,CarlaM, et al. Rapid expansion of fecycling stem cells in cultrues of plastic-adheren cells from human bone marrow[J]. Proc Natl Aca SciUSA, 2000, 97(7): 3213-3218.
35. Heaney NB, Holyoake TL. Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol. 2007 Jun;25(2):66-75.
36. Spencer A, Jackson J, Baulch-Brown C. Enumeration of bone marrow 'homing' haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation. Bone Marrow Transplant. 2001 Dec;28(11):1019-22.
37. Roberts AW. G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors. 2005 Mar;23(1):33-41.
38. Vianello F, Dazzi F. Mesenchymal stem cells for graft-versus-host disease: a double edged sword? Leukemia. 2008 Mar;22(3):463-5. No abstract available.
39. Beyer NN, da Silva ML. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol, 2006; (174): 249-282.
40. Delorme B, Charbord P. Culture and characterization of human bone marrow mesenchymal stem cells. Methods Mol Med. 2007;140:67-81.
41.邓均,粟永萍.骨髓间充质干细胞可塑性研究.生理科学进展, 2007; 38(2): 133-135
42. Yang XS, Wu HX, Xiao B. Human mesenchymal stem cells differentiate into neuron-like cells and show SMN protein expression. Zhonghua Yi Xue Za Zhi, 2005, 85(16): 1125-1128.
43.邓均,艾国平,粟永萍等. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
44. Yim EK, Pang SW, Leong KW. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res. 2007 May 15;313(9):1820-1829.
45. Inoue K, Noda S, Ogonuki N, et al. Differential developmental ability of embryos cloned from tissue-specific stem cells. Stem Cells. 2007 May;25(5):1279-1285.
46. Satake K, Lou J, Lenke LG, et al. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine. 2004; 29(18): 1971-1979.
47. Qi X, Yang DL, Qi F, et al. Statistical analysis on 2213 inpatients with traffic injuries from January 2003 to September 2005 in Ningbo city. Chin J Traumatol. 2006 Aug;9(4):228-33.
48. Odebode TO, Ologe FE. Facial nerve palsy after head injury: Case incidence, causes, clinical profile and outcome. J Trauma. 2006 Aug;61(2):388-91.
49. Lee KS. Estimation of the incidence of head injury in Korea: an approximation based on national traffic accident statistics. J Korean Med Sci. 2001 Jun;16(3):342-6.
50. Itoh T, Satou T, Nishida S, et al. Immature and mature neurons coexist among glial scars after rat traumatic brain injury. Neurol Res. 2007 Oct;29(7):734-42.
51. Kovesdi E, Czeiter E, Tamas A, et al. Rescuing neurons and glia: is inhibition of apoptosis useful? Prog Brain Res. 2007;161:81-95.
52. Rink A,Fung KM, Trejanouski JQ,et al. Evidence of apoptosis cell death after experience traumatic brain injury in the rat. Am J Pathol, 1995; 147(6):1575-1589
53. Tashlykov V, Katz Y, Gazit V, et al. Apoptotic changes in the cortex and hippocampus following minimal brain trauma in mice. Brain Res. 2007 Jan 26;1130(1):197-205.
54. Morrison B, Cater HL, Benham CD, et al. An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures. J Neurosci Methods. 2006 Jan 30;150(2):192-201.
55. Fischer C, Mutschler V. Traumatic brain injuries in adults: from coma to wakefulness. Neurophysiological data. Ann Readapt Med Phys. 2002 Nov;45(8):448-55.
56. Mac Donald CL, Dikranian K, Bayly P, et al. Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci. 2007 Oct 31;27(44):11869-76.
57. Marmarou A, Montasser PD, Foda AE, et al. A new model of diffuse brain injury in rats [J]. J Neurosurg, 1994, 80: 291-300.
58. Bederson JB, Pitts LH, Tsuji M, et a1. Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination [J]. Stroke, 1986, 17(3):472-476.
59. Shapira Y, Lam AM, Eng CC, et a1. Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury [J]. Stroke, 1994, 25(8): 1637-1643.
60. Langlois JA, Rutland B W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):375-8.
61. Shindo T, Matsumoto Y, Wang Q, et al. Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury. J Med Invest. 2006 Feb;53(1-2):42-51.
62. Boockvar JA, Schouten J, Royo N, et al. Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery. 2005;56(1):163-71.
63. Hahn JY, Cho HJ, Kang HJ, et al. Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol. 2008 Mar 4;51(9):933-43.
64. Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007 Oct;25(10):2648-59.
65. Lévesque JP, Winkler IG, Larsen SR, et al. Mobilization of bone marrow-derived progenitors. Handb Exp Pharmacol. 2007;(180):33-6.
66. Li H, Fu X, Ouyang Y, et al. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res. 2006 Dec;326(3):725-36.
67. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Zhonghua Yi Xue Za Zhi. 2005 Jul 20; 85(27): 1883-1884.
68. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb;25(2):371-379.
69. Sun AN, Wu DP, Wang Y, et al. Clinical study on haploid HLA-matched hematop-oietic stem cell transplantation for treatment of malignant hematological disease [J]. Ai Zheng, 2006, 25(8): 1019-1022.
70. Frangoul H, Nemecek ER, Billheimer D, et al. A prospective study of G-CSF primed bone marrow as a stem-cell source for allogeneic bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium (PBMTC) study. Blood. 2007 Dec 15;110(13):4584-7.
71. Gomez RC, Pinto MA, Gonzalez BM. Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia[J]. Clin Transl Oncol, 2006, 8(10): 729-734.
72. Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26.
73. Tigue CC, McKoy JM, Evens AM, et al. Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant. 2007 Aug;40(3):185-92.
74. Von AS, Hartung T. Potential for immune reconstitution through G-CSF treatment of HIV patient s [J]. Arch Immunol Ther Exp (Warsz), 2002, 50(2): 111-120.
75. Marshall JC. The effects of granulocyte colony-stimulating factor in preclinical models of infection and acute inflammation. Shock. 2005 Dec;24 Suppl 1:120-9.
76. Lehrke S, Mazhari R, Durand DJ, et al. Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circ Res, 2006; 99(5): 553-560.
77. Sokolova IB, Fedotova OR, Zin'kova NN, et al. Effect of mesenchymal stem cell transplant- ation on cognitive functions in rats with ischemic stroke. Bull Exp Biol Med. 2006 Oct;142(4):511-4.
78. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects ofgranulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
79. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
80. Woei CS, Shinn ZL, Hui YB, et al. Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor Stimulated Stem Cells. Circulation. 2004, 28;110(13):1847-54.
81. UrdzíkováL, JendelováP, GlogarováK,et al. Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma. 2006 Sep;23(9):1379-91.
82. Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005 Aug;33(2):145-52.
83. Shyu WC, Lee YJ, Liu DD, et al. Homing genes, cell therapy and stroke. Front Biosci. 2006 Jan 1;11:899-907.
84. Obeyesekere MN, Berry RW, Spicer PP, et al. A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization into the peripheral blood. Cell Prolif. 2004 Aug;37(4):279-94.
85. Lee C, Evans CA, Spooncer E, et al. Generation of a conditionally immortalized myeloid progenitor cell line requiring the presence of both interleukin-3 and stem cell factor to survive and proliferate. Br J Haematol. 2003 Sep;122(6):985-95.
86. Nadri S, Soleimani M, Hosseni RH, et al. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol. 2007;51(8):723-9.
87. Meirelles Lda S, Nardi NB. Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br J Haematol. 2003 Nov;123(4):702-11.
88. Cho HJ, Kim TY, Cho HJ, et al. The effect of stem cell mobilization by granulocyte-colony stimulating factor on neointimal hyperplasia and endothelial healing after vascular injury with bare-metal versus paclitaxel-eluting stents. J Am Coll Cardiol. 2006 Jul 18;48(2):366-74.
89. Viswanathan A, Painter RG, Lanson NA et al. Functional expression of N-formyl peptide receptors in human bone marrow-derived mesenchymal stem cells. Stem Cells. 2007 May;25(5):1263-9.
90. Kimura A, Ohmori T, Ohkawa R, et al. Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells. 2007 Jan;25(1):115-24.
91. Zhao J, Moore AN, Redell JB, et al. Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci. 2007 Sep 19;27(38):10240-8.
92. Habgood MD, Bye N, Dziegielewska KM, et al. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci. 2007 Jan;25(1):231-8.
93. Burt D, Salvidio G, Tarabra E, et al. The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes. Am J Pathol. 2007 Dec;171(6):1789-99.
94. Ishida Y, Kimura A, Kondo T, et al. Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration. Am J Pathol. 2007 Mar;170(3):843-54.
95. Schmal H, Niemeyer P, Roesslein M, et al. Comparison of cellular functionality of human mesenchymal stromal cells and PBMC. Cytotherapy. 2007;9(1):69-79.
96. Goings GE, Sahni V, Szele FG. Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 2004; 96(2): 213-226
97. Czarnowska E, Gajerska-DM, Ku?mierski K, et al. Expression of SDF-1-CXCR4 axis and an anti-remodelling effectiveness of foetal-liver stem cell transplantation in the infarcted rat heart. J Physiol Pharmacol. 2007 Dec;58(4):729-44.
98. Nagasawa T. The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche. Adv Exp Med Biol. 2007;602:69-75.
99. Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008 Jan;15(1):49-58.
100.Ratajczak MZ, Zuba-Surma E, Kucia M, et al. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006 Nov;20(11):1915-24.
101.Bhakta S, Hong P, Koc O. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med. 2006 Jan-Mar;7(1):19-24.
102.T?gel F, Isaac J, Hu Z, et al. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005 May; 67(5): 1772-84.
103.Lobanov AV, Uzdenski? AB. Neutrophin NGF protects glial cells, but not stretch receptor neurons of the crayfish Astacus astacus from photooxidative stress. Zh Evol Biokhim Fiziol. 2007 Sep-Oct;43(5):448-9.
104.Zhou HL, Yang HJ, Li YM, et al. Changes in Glial Cell Line-derived Neurotrophic Factor Expression in the Rostral and Caudal Stumps of the Transected Adult Rat Spinal Cord. Neurochem Res. 2008 May;33(5):927-37.
105.Wei D, Jin Z, J?rlebark L, et al. Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro. Dev Neurobiol. 2007 Jan;67(1):108-22.
106.Steinmetz CC, Buard I, Claudepierre T, et al. Regional variations in the glial influence on synapse development in the mouse CNS. J Physiol. 2006 Nov 15;577(Pt 1):249-61.
1. Burgess A, Metcalf D. Characterization of a serum factor stimulating the differentia- tion of myelomonocytic leukemia cells[J] . Int J Cancer, 1980, 26 (5): 647-651.
2. Kuderer NM, Dale DC, Crawford J, et al. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. 2007 Jul 20; 25(21): 3158-3167.
3. Donini M, Fontana S, Savoldi G, et al. G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007 Jun 1;109(11):4716-4723.
4. Kurdi M, Booz GW. G-CSF-based stem cell therapy for the heart-unresolved issues part A: paracrine actions, mobilization, and delivery. Congest Heart Fail. 2007 Jul-Aug; 13(4): 221-227.
5. Sehara Y, Hayashi T, Deguchi K, et al. Potentiation of neurogenesis and angiogenesis by G-CSF after focal cerebral ischemia in rats. Brain Res. 2007 Jun 2; 1151:142-149.
6. Piscaglia AC, Shupe TD, Oh SH, et al. Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats. Gastroenterology. 2007 Aug; 133(2): 619-631.
7. Boneberg EM ,Hartung T. Molecular aspects of anti-inflammatory action of G-CSF[J ] . Inflamm Res, 2002, 51 (3): 119-128.
8. Hoglund M. Glycosylated and non-glycosylated recombinant man granulocyte colony-stimulating factor ( rhG-CSF)-what difference ? [J] . Med Oncol, 1998, 15 (4): 229-233.
9. Layton JE, Hall NE. The interaction of G-CSF with its receptor [J]. Front Biosci, 2006, 1 (11): 3181-3189.
10. Sun AN, Wu DP, Wang Y, et al. Clinical study on haploid HLA-matched hematop- oietic stem cell transplantation for treatment of malignant hematological disease [J]. Ai Zheng, 2006, 25(8): 1019-1022.
11. Gomez RC, Pinto MA, Gonzalez BM. Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia[J]. Clin Transl Oncol, 2006, 8(10): 729-734.
12. Von AS, Hartung T. Potential for immune reconstitution through G-CSF treatment of HIV patient s [J]. Arch Immunol Ther Exp (Warsz), 2002, 50(2): 111-120.
13. Murry CE, Wiseman RW, Schwartz SM, et al. Skeleta myoblast trans-plantation for repair of myocardial necrosis [J]. J Clin Invest, 1996, 98: 2512-2523.
14. Kajstura J, LeriA, Finato N, et al. Myocyte p roliferation in end-stage cardiac failure in humans [J]. Proc Natl Acad Sci USA, 1998, 2195(15): 8801-8805.
15. Beltermi AP, Urbanek, KajsturaJ, et al. Evidence that human cardiacmyocytes divide aftermyocardial infarction[J]. N Engl JMed, 2001, 344(23): 1750-1774.
16. Ieishi K, Nomura M, Kawano T, et al. The effect of G-CSF in a myocardial ischemia reperfusion model rat. J Med Invest. 2007 Feb; 54(1-2): 177-183.
17. Muller P, Pfeiffer P, Koglin J, et al. Cardiomyocytes of noncardiac origin in myocardial biop sies of human transp lanted hearts [J]. Circulation, 2002, 106 (1): 31-35.
18. Bittira B, Shum TD, Khaldi A, et al. Mobilization and homing of bone marrow stromal cells in myocardial infarction[J]. Eur J Cardio - thorac Surg, 2003, 24(3): 393-398.
19. CiullaM M, Lazzari L, Pacchiana R, et al. Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury [J]. Haematologica, 2003, 88 (6): 614-621.
20. Bittira B, Shum T im D, Khaldi A. Mobilization and hom ing of bone marrow stromalcells in myocardial infarction. Euro J Cardio Tho rac Surg,2003, 24:393-398.
21. KocherA A, SchusterM D, Szabo MJ, et al. Neovascularization of ischemia myocardium by human bone marrow derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and imp roves cardiac function[J]. N at Med, 2001, 7: 430-436.
22. Assmus B, Schach V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction ( TOPCARE AM I)[J]. Circulation, 2002, 106: 3009-3017.
23. Fuch S, Baffou R, Zhou YF, et al. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia[J]. JACC, 2001, 37: 1726-1732.
24. Stauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans[J]. Circulation, 2002, 106: 1913-1918.
25. Wang JS, Shum TD, Chedrawy E, et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications [J]. J Tho rac Cardiovasc Surg, 2001, 122: 699-705.
26. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival[J]. P roc N atl A cad Sci, 2001, 98: 10344-10349.
27. Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell, 2002, 109(5): 625-637.
28. Deten A, Volz HC, BriestW, et al. Cardiac cytokineexp ression is up regulated in the acute phase after myocardial infarction: experimental study in rats[J]. Cardiovasc Res, 2002, 55(2): 329-340.
29. Pillarisetti K, Gupta SK. Cloning and relative expression analysis of rat stromal cell derived factor-1 ( SDF-1) , 1: SDF-1-mRNA is selectively induced in rat model of myocardial infarction [J]. Inflammation, 2001, 25(5) : 293-300.
30. Peled A, KolletO, Ponomaryov T, et al. The chemokine SDF-1 activates the integrins LFA-1,VLA-4, and VLA-5 on immature human CD34+ cells: role in transendothelial/stromal migration and engraftment of NOD /SCID mice[J]. Blood, 2000, 95(11): 3289-3296.
31. Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 onstem-cell homing and tissue regeneration in Ischaemic cardiomyopathy[J]. Lancet, 2003, 362(9385): 697-703.
32. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infracted heart, improving function and survival[J]. Proc NatlAcad Sci, 2001, 98 (18): 10344-10349.
33. Miki T, Sakamoto J, Nakano A, et al. Mobilization of bone marrow cells by G-CSF /M-CSF improves ventricular function in the heart undergoing post-infarct remodeling [J]. Circulation, 2002, 106: 15.
34. Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by granulocyte macrophage colony-stimulating factor in patients with coronary artery disease a randomized, double-blind, place bo-controlled study[J]. Circulation, 2001, 104(17): 2012-2017.
35. Kuethe F, Figulla HR, VothM, et al. Mobilization of stem cells by granulocyte colony-stimulating factor for there generation of myocardial tissue after myocardial infarction [J]. Dtsch Med Wochenschr, 2004, 129(9): 424-428.
36. Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improve damaged heart function [J]. Circulation, 1999, 100(19 supp l): 247-256.
37. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium[J]. Nature, 2001, 410(6829): 710-715.
38. Li L, Takemura G, Li Y, et al. Granulocyte colony-stimulating factor improves left ventricular function of doxorubicin-induced cardiomyopathy. Lab Invest. 2007 May; 87(5): 440-455.
39. Kocher AA, SchusterM D, SzabolcsM J, et al. Neovascularization of ischemicmyo- cardium by human bone marrow derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. NatMed, 2001, 7 (4): 430-436.
40. Gould E, Reeves AJ, Graziano MS, et al. Neurogenesis in the neocortex of adult primates. Science, 1999, 286: 548-552.
41. Zhang RL, Zhang ZG, Zhang L, et al. Proliferation and differentiation of progenitorcells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience, 2001, 105: 33-41.
42. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
43. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bonemarrow cells repair the infarcted heart, imp roving function and survival. Proc Natl Acad Sci USA, 2001, 98: 10344-10349.
44. Six I, Gasan G, Mura E, et al. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. Eur J Pharmacol, 2003, 458: 327-328.
45. Corti S, Locatelli F, Strazzer S, et al. Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment. Exp Neurol, 2002, 177: 443-452.
46. Gu W, Brannst om T, Wester P. Cortical neurogenesis in adult rat safter reversible photothrombotic stroke [J]. J Cereb Blood Flow Metab, 2000 ,20(8):1166-1173.
47. Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice[J]. Nature, 2000, 405(6789): 951-955.
48. Abe K. Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury [J]. J Cereb Blood Flow Metab, 2000, 20(10): 1393-1408.
49. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neurogenesis[J]. J Clin Invest, 2005, 115(8): 2083-2098.
50. Mahmood A, Lu D, Chopp M. Intravenous administ ration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury [J]. J Neurotrauma, 2004, 21(1):33-39.
51.邓均,艾国平,粟永萍. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
52.邓均,艾国平,粟永萍. G-CSF动员循环间充质干细胞及其对颅脑损伤修复的可行性分析.第三军医大学学报. 2007; 29(12): 1131-1134.
53. Hintzen RQ, Voormolen J, Sonneveld P, et al. Glioblastoma causing granulocytosis by secretion of granulocyte colony-stimulating factor[J]. Neurology, 2000, 54 (1): 259-261.
54. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stoke, 2003, 34(3): 745-751.
55. Da SN, Meyer MS, Menot ML, et al. G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8 ;21)translocation: basis for potential therapeutic efficacy[J]. Cytokines Cell Mol Ther, 1997, 3(2): 75-78.
56. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulo- cyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003, 34 (3): 745-751.
57. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteract sprogrammed cell death and drives neurogenesis. J Clin Invest [J]. Epub, 2005, 115(8): 2083-2098.
58. Mahmood A, Lu D, Chopp M. Intravenous administ ration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury[J]. J Neurot rauma, 2004, 21(1): 33-39.
59. Heard SO, Fink MP. Counter regulatory control of the acute inflammatory response: granulocyte colony-stimulating factor has anti-inflammatory properties[J]. Crit Care Med, 1999, 27: 1019-1021.
60. Heard SO, Fink MP, Gamelli RL, et al. Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute t rumatic brain injury or cerebral hemorrhage: the filgrastin study group[J]. Crit Care Med, 1998, 26:748-754.
61. Hebert JC, O’Reilly M, Gamelli RL. Protective effect of recombinant human gran- ulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice[J].Arch Surg, 1990, 125: 1075-1078.
62. Ihle JN. STATs: signal transducers and activators of transcription[J]. Cell, 1996, 84: 331-334.
63. Gibson CL, Jones NC, Prior MJ, et al. G-CSF suppresses edema formation and reduces interleukin-1βexpression after cerebral ischemia in mice[J]. J Neuropathol Exp Neurol, 2005, 64: 763-769.
64. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003, 34: 745-751.
65. Graham SH, Chen J, Clark RS. Bcl-2 family gene products in cerebral ischemia and traumatic brain injury[J]. J Neurotrauma, 2000, 17:831-841.
66. Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt[J]. Science, 1997, 275: 661-665.
67. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis[J]. J Clin Invest, 2005, 115:2083-2098.
68. Chen J, Li Y, Katakowski M, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous ell proliferation after stroke in female rat[J]. J Neurosci Res, 2003, 73:778-786.
69. Krupinski J, Kaluza J, Kumar P, et al. Role of angiogenesis in patients with cerebral ischemic stroke[J]. Stroke, 1994, 25: 1794-1798.
70. Ca?izo MC, Lozano F, González-Porras JR, et al. Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. Cytotherapy. 2007;9(1):99-102.
71. Zhou B, Cao XC, Fang ZH, et al. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells. Acta Pharmacol Sin. 2007 Jan;28(1):89-97.
72. Cella G, Marchetti M, Vignoli A, et al. Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor. Leukemia. 2006 Aug;20(8):1430-4.
73. Takahashi T, Kalka C, Masuda H, et al. Ischemia and cytokine induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. [J]. Nat Med, 1999, 5(4): 434-438.
74. Lee ST, Chu K, Jung KH, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia [J]. Brain Res, 2005, 1058(1/2): 120- 128.
75. Shyu WC, Lin SZ, Yang HI, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells[J]. Circulation, 2004, 110:1847-1854.
76. Lataillade JJ, Clay D, Dupuy C, et al. Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival[J]. Blood, 2000, 95: 756-768.
77. Czarnowska E, Gajerska-DM, Ku?mierski K, et al. Expression of SDF-1-CXCR4 axisand an anti-remodelling effectiveness of foetal-liver stem cell transplantation in the infarcted rat heart. J Physiol Pharmacol. 2007 Dec;58(4):729-44.
78. Nagasawa T. The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche. Adv Exp Med Biol. 2007;602:69-75.
79. Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008 Jan;15(1):49-58.
80. Ratajczak MZ, Zuba-Surma E, Kucia M, et al. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006 Nov;20(11):1915-24.
81. Lachmund A, Gehrke D, Krieglstein K, et al. Trophic factors from chromaffin granules promote survival of peripheral and central nervous system neurous[J]. Neuroscience, 1994, 62: 361-370.
82. Cohen CS, Fraser SE. Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature, 1995, 378: 192-196.
83. Kang H, Schuman EM. Long-lasting neurotrophininduced enhancement of synaptic transmission in the adult hippocampus[J]. Scince, 1995, 267: 1658-1662.
84. Lindholm D. Neurotrophic factors and neuronal plasticity: is there a link[J]? Adv Neurol, 1997, 73: 1-6.
85. Wang Y, Lin SZ, Chiou AL, et al. Glial cell linederived neurotrophic factor protects against ischemiainduced injury in the cerebral cortex[J]. J Neurosci, 1997, 17: 4341-4348.
86. Li Y, Chen J, Chen XG, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery[J]. Neurology, 2002, 59: 514-523.
87. Stratos I, Rotter R, Eipel C, et al. Granulocyte-colony stimulating factor (G-CSF) enhances muscle proliferation and strength following skeletal muscle injury in rats. J Appl Physiol. 2007 Aug 23; [Epub ahead of print]
88. Dirsch O, Chi H, Gu YL, et al. Influence of stem cell mobilization and liver regeneration on hepatic parenchymal chimerism in the rat. Transplantation. 2006 Jun 27;81(12):1695-1699.
89. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver.Bull Exp Biol Med. 2005 Nov;140(5):644-647.
90. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res. 2006 Mar 15; 12(6): 1804-1812.
91.邓均,粟永萍.骨髓间充质干细胞可塑性研究.生理科学进展, 2007; 38(2): 133-135.
92. Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005 Jul 15;106(2):756-763.
1. Chan BP, Hui TY, Yeung CW, et al. Self-assembled collagen-human mesenchymal stem cell microspheres for regenerative medicine. Biomaterials. 2007; 28(31): 4652-4666.
2. Guo CA, Liu XG, Huo JZ, et al. Novel gene-modified-tissue engineering of cartilage using stable transforming growth factor-beta1-transfected mesenchymal stem cells grown on chitosan scaffolds. J Biosci Bioeng. 2007; 103(6): 547-556.
3. Tiina M, Jarmo L. Placenta—an alternative source of stem cells . Toxicology and Applied Pharmacology 2005; 207( 2): 544-549.
4. Amy C, Eric DL, Gregory M, et al. Fusion of neural stem cells in culture. Experimental Neurology 2006; 198( 1): 129-135.
5. David CC,Reiner C,CarlaM, et al. Rapid expansion of fecycling stem cells in cultrues of plastic-adheren cells from human bone marrow[J]. Proc Natl Aca SciUSA, 2000, 97(7): 3213-3218.
6. Pittenger F, Mackay A, Beck S, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411): 143-147.
7. Bruder SP, Jaiswal N, Haynesworth SE, et al. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subculativation and following cryopreser-vation[J].J Cell Biochem, 1997, 64(2): 278-294.
8. Lennon DP, Haynesworth SE, Young RG, et al. A chemically defined medium supprots in vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem cells[J]. Exp cell Res, 1995, 219(1): 211-222.
9. Conget PA, Minguell JJ. Phenotypical and functional properties of huamn bone marrow mesenchymal progenitor cells[J]. J Cell Physiol, 1999, 181(1): 67-73.
10.Tsai MS, Hwang SM, Tsai YL,et al. Clonal Amniotic Fluid-Derived Stem Cells Express Characteristics of Both Mesenchymal and Neural Stem Cells[J]. Biol Reprod, 2006, 74(10): 545-551.
11.Shih DT, Lee DC, Chen SC, et al. Isolation and Characterization of Neurogenic Mesenchymal Stem Cells in Human Scalp Tissue[J]. Stem Cells, 2005, 23(7):1012-1020.
12.Okamoto T, Aoyama T, Nakayama T, et al. Clonal heterogeneity in differenti- ation potential of immortalized human mesenchymal stem cells[J]. Biochem Biophys Res. Commun. 2002, 295(2): 354-361.
13.Muraglia A, Cancedda R, Quarto R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model[J]. J Cell Sci, 2000, 113(7): 1161-1166.
14.Conget PA, Mingguell JJ. Phenotypical and functional propertyes of human bone marrow mesenchymal progenitor cells[J] . J Cell Physiol, 1999, 181(1): 67-73.
15.Pittingger MF, Mackaya M, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J] . Science, 1999, 284(5411): 143-147.
16.Bruder SP, Ricalton NS, Boynton RE, et al. Mesenchymal stem cell surface antigen SB - 10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation[J] . J Bine Miner Res, 1998, 13(3): 655- 663.
17.Martinez C, Hofmann TJ, Marino R, et al. Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood. 2007 May 15; 109(10): 4245-4248.
18.Assia D, Geraldine LP, David JH, et al. Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells 2006; 10(9): 1634-1646.
19.Richardson LE, Dudhia J, Clegg PD, et al. Stem cells in veterinary medicine - attempts at regenerating equine tendon after injury. Trends Biotechnol. 2007 Aug 8; [Epub ahead of print]
20.Velloso CP, Simon A, Brockes JP. Mammalian postmitotic nuclei reenter the cell cycle after serum stimulation in new t/mouse hybrid myotubes. CurrBiol, 2001, 11(11): 855-858.
21.Kadiyala S, Young RG, Thide MA. Culture expanded ecanine mesenchymal stem cells possess osteochon drogenic potenial in vivo and in vitro[J].Cell Transplant,1997,6: 123-134.
22.Weike Si, Quan Kang, Hue HL, et al. CCN1/Cyr61 Is Regulated by the Canonical Wnt Signal and Plays an Important Role in Wnt3A-Induced Osteoblast Differentiation ofMesenchymal Stem Cells[J]. Mol.Cell.Biol., 2006, 26(8): 2955 - 2964.
23.Leonard JF, Patricia AZ, Chen Li, et al. Differential Expression Profiling of Membrane Proteins by Quantitative Proteomics in a Human Mesenchymal Stem Cell Line Undergoing Osteoblast Differentiation[J]. Stem Cells, 2005, 23(10): 1367-1377.
24.Angele P, Kajat R, Nerlich M, et al. Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin compostte sponge[J]. Tissue Eng, 1999, 5(6): 545-554.
25.Majumdar MK, Valeerit B, Pduso DP, et al. Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells[J]. J Cell Physiol, 2000, 185(1): 98-106.
26.Yonggang Pang, Pengcheng Cui, Wenxian Chen, et al. Quantitative Study of Tissue- Engineered Cartilage With Human Bone Marrow Mesenchymal Stem Cells[J]. Arch Facial Plast Surg, 2005,7(1): 7-11.
27.WakitaniS, SaitoT, CaplanAI, et al. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5 azacytidine[J]. Muscle Nerve, 1995, 18(12): 1417-1426.
28.Wakitania S, Satio T, Caplan AL. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J]. Muscle Nervd, 1995, 18(12): 1417-1426.
29.Ferrari G, Cusella DE, Angelis G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors[J]. Science, 1998, 279(5356): 1528-1530.
30.Wang JS, Shum T, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty feasibility and potential clinical advantages[J]. J Thorac Careiovasc Surg, 2000, 120(5): 999-1005.
31.Wangde Dai, Sharon LH, Bradley JM, et al. Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium: Short- and Long-Term Effects[J]. Circulation, 2005, 112(5): 214-223.
32.邓均,艾国平,粟永萍. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
33.Yang XS, Wu HX, Xiao B. Human mesenchymal stem cells differentiate into neuron-like cells and show SMN protein expression. Zhonghua Yi Xue Za Zhi, 2005,85(16): 1125-1128.
34.Yim EK, Pang SW, Leong KW. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res. 2007 May 15;313(9):1820-1829.
35.Inoue K, Noda S, Ogonuki N, et al. Differential developmental ability of embryos cloned from tissue-specific stem cells. Stem Cells. 2007 May;25(5):1279-1285.
36.Den YB, Yuan QT, Liu XG, et al. Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons. Chin Med J (Engl), 2005, 118(18): 1533-1541.
37.Cho KJ, Trzaska KA, Greco SJ, et al. Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha. Stem Cells, 2005, 23(3): 383-391.
38.Kopen GC, Prockop DJ, Phinney DG, el at. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proc Natl Acad Sci,1999, 96(19): 10711-10716.
39.Brazelton TR, RossiFM, Keshet GL, et al. From marrow to brain: expression of neuronal phenotypes in adult mice[J]. Science, 2000, 290(5497): 1775-1779.
40.Chen J,Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats[J]. Stroke, 2001, 32(4): 1005-1011.
41.Bae JS, Furuya S, Shinoda Y, et al. Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice. Hum Gene Ther, 2005, 16(8): 1006-1011.
42.Zhang WW, Guo ZK. Problematic issues in clinical trials of mesenchymal stem cells and unraveling strategies-review. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):901-904.
43.Oh SH, Miyazaki M, Kouchi H, et al. Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro[J]. Biochem Biophys Res Com, 2000, 279(2):500-504.
44.Hong SH, Gang EJ, Jeong JA, et al. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem BiophysRes Commun, 2005, 330(4): 1153-1161.
45.Theise ND, Badves, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation[J]. Hepatology, 2000, 31(1): 235-240.
46.Wang JS, Shunrtim D, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages[J]. J Thora Cardiova Surg, 2000, 120(3): 999-1006.
47.Terai S, Sakaida I, Yamamoto N, et al. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes[J]. J Biochem, 2003, 134(4):551-558.
48.Yamamoto N, Terai S, Ohata S, et al. A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8,is useful for cell therapy to repair damaged liver[J]. Biochem Biophys Res Com, 2004, 313(4): 1110-1118.
49.Marina M, Barbara I, Carla Z, et al. Mesenchymal Stem Cells Are Renotropic, Helping to Repair the Kidney and Improve Function in Acute Renal Failure[J]. J Am Soc Nephrol. 2004, 15(7): 1794-1804.
50.Mauricio R, Jianguo X, Charles R, et al. Bone Marrow–Derived Mesenchymal Stem Cells in Repair of the Injured Lung. Am J Respir Cell Mol Biol, 2005, 33(2): 145-152.
51.Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007 Oct 4;449(7162):557-63.
52.Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells. 2007 Nov;25(11):2896-902. Epub 2007 Sep 27.
53.Chen XD, Dusevich V, Feng JQ, et al. Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res. 2007 Dec;22(12):1943-56.
54.Lin S, Rocky ST. Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow. FASEB J 2004; 10(4): 1096-1100.
55.Orkin SH, Zon L I. Hematopoiesis and stem cells : plasticity versus developmental heterogeneity. Nat Immunol 2002; 3(2): 323-328.
56.Rubio D, Garcia S, Paz MF, et al. Molecular characterization of spontaneousmesenchymal stem cell transformation. PLoS ONE. 2008 Jan 2;3(1):e1398.
57.Roubelakis MG, Pappa KI, Bitsika V, et al. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev. 2007 Dec;16(6):931-52.
58.Naujokat C, Sari? T. Concise review: role and function of the ubiquitin-proteasome system in mammalian stem and progenitor cells. Stem Cells. 2007 Oct;25(10):2408-18.
59.Maya S, Jennifer C, Jayme S, et al. Cell-Cell Fusion Induced by the Avian Reovirus Membrane Fusion Protein Is Regulated by Protein Degradation. J. Virol 2004; 78(11): 5996-6004.
60.Oliveri RS. Epigenetic dedifferentiation of somatic cells into pluripotency: cellular alchemy in the age of regenerative medicine? Regen Med. 2007 Sep;2(5):795-816.
61.Paulis M, Bensi M, Orioli D, et al. Transfer of a human chromosomal vector from a hamster cell line to a mouse embryonic stem cell line. Stem Cells. 2007 Oct;25(10):2543-50.
62.Nunes VA, Cava?ana N, Canovas M, et al. Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro only after exposure to in vivo muscle environment. Biol Cell. 2007 Apr;99(4):185-96.
63.Ying QL, Nichols J, Evans EP, et al. Changing potency by spontaneous fusion. Nature, 2002 , 416 (6880): 485-487.
64.Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002, 416(6880): 542-545.
65.Nichols J, Zevnik B, Anastassiadis K ,et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 1998, 95(3): 379-391.
66.Lysdahl H, Gabrielsen A, Minger SL, et al. Derivation and characterization of four new human embryonic stem cell lines: the Danish experience. Reprod Biomed Online. 2006 Jan;12(1):119-26.
67.Gibson TC, Pei Y, Quebedeaux TM, et al. Mitochondrial DNA deletions in primate embryonic and adult stem cells. Reprod Biomed Online. 2006 Jan;12(1):101-6.
68.Park YB, Kim YY, Oh SK, et al. Alterations of proliferative and differentiationpotentials of human embryonic stem cells during long-term culture. Exp Mol Med. 2008 Feb 29;40(1):98-108.
69.Jiang Y, Jahagirdar B, Reinhardt RL, et al. Pluripotecy of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418: 41-49.
70.Zipori D. The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther. 2006 Jan;1(1):95-102.
71.Siebert S, Anton-Erxleben F, Bosch TC. Cell type complexity in the basal metazoan Hydra is maintained by both stem cell based mechanisms and transdifferentiation. Dev Biol. 2008 Jan 1;313(1):13-24.
72.Clarke AR, Meniel V. The intestinal stem cell niche studied through conditional transgenesis. Ernst Schering Found Symp Proc. 2006;5:99-108.
73.Chen Y, Shao JZ, Xiang LX, et al. Mesenchymal stem cells: A promising candidate in regenerative medicine. Int J Biochem Cell Biol. 2008;40(5):815-20.
74.Ferrari M, Corradi A, Lazzaretti M, et al. Adult stem cells: perspectives for therapeutic applications. Vet Res Commun. 2007 Aug;31 Suppl 1:1-8.
1. Beschorner R, Dietz K, Schauer N, et al. Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol Histopathol, 2007; 22(5): 515-526.
2. Rink A, Fung KM, Trejanouski JQ, et al. Evidence of apoptosis cell death after experience traumatic brain injury in the rat. Am J Pathol, 1995; 147(6): 1575-1589
3. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
4. Ke Y, Chi L, Xu R, et al. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells. 2006; 24(4): 1011-1019.
5. Satake K, Lou J, Lenke LG, et al. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine. 2004; 29(18): 1971-1979.
6. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Chinese Medical Journal. 2005 Jul 20; 85(27): 1883-1884.
7. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb; 25(2):371-379.
8. Gutierrez-RM, Reyes-ME, Mayani H, ea al. Characterization of the adherent cells developed in Dexter-type long-term cultures from human umbilical cord blood. Stem Cells. 2000; 18: 46-52.
9. Lee MW, Choi J, Yang MS, et al. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2004; 320: 273-278.
10. Zvaifler NJ, Marinova-ML, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000; 2: 477-488..
11. Wu GD, Nolta JA, Jin YS, et al. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation. 2003; 75: 679-685.
12. Lazarus HM, Haynesworth SE, Gerson SL, et al. Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother. 1997; 6: 447-455.
13. Wexler SA, Donaldson C, Denning KP, et al. Adult bone marrow is a rich source of human mesenchymal’stem’cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003; 121: 368-374.
14. Chen J, Larochelle A, Fricker S, Bridger G, Dunbar CE, Abkowitz JL. Mobilization as a preparative regimen for hematopoietic stem cell transplantation. Blood. 2006; 107(9): 3764-3771.
15. Robinson SN, Pisarev VM, Chavez JM, et al . Use of matrix metalloproteinase (MMP)-9 knockout mice demonstrates that MMP-9 activity is not absolutely required for G-CSF or Flt-3 ligand-induced hematopoietic progenitor cell mobilization or engraftment. Stem Cells. 2003; 21(4): 417-427.
16. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects ofgranulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
17. Lehrke S, Mazhari R, Durand DJ, et al. Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circ Res, 2006; 99(5): 553-560.
18. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
19. Marmarou A, Montasser PD, Foda AE, et al. A new model of diffuse brain injury in rats [J]. J Neurosurg, 1994, 80: 291-300.
20. Bederson JB, Pitts LH, Tsuji M, et a1. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination [J]. Stroke, 1986, 17(3): 472-476.
21. Shapira Y, Lam AM, Eng CC, et a1. Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury [J]. Stroke, 1994, 25(8): 1637-1643.
22. Beyer NN, da Silva ML. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol, 2006; (174): 249-282.
23. Kassis I, Zangi L, Rivkin R, et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006; 37(10): 967-976.
24. Zhang Y, Liang JL, Wang S, et al. Autologous bone marrow stromal cell transplantation with application of granulocyte colony-stimulating factor improves rabbit cardiac performance after acute myocardial infarction. Journal of Southern Medical University. 2007; 27(1): 43-45.
25. Ozaki K, Sato K, Oh I, et al. Mechanisms of immunomodulation by mesenchymal stem cells. Int J Hematol. 2007 Jul; 86(1): 5-7.
2. Beschorner R, Dietz K, Schauer N, et al. Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol Histopathol, 2007; 22(5): 515-26.
3. BauzáG, Lamorte WW, Burke PA, et al. High mortality in elderly drivers is associated with distinct injury patterns: analysis of 187,869 injured drivers. J Trauma. 2008 Feb; 64(2):304-10.
4.郑文贵,李向云. 1996～2003年全国交通事故伤害的时间序列分析.中国卫生事业管理,2006; 2:105-7.
5. Baker AJ, Park E, Hare GM, et al. Effects of resuscitation fluid on neurologic physiology after cerebral trauma and hemorrhage. J Trauma. 2008 Feb;64(2):348-57.
6. Kraus MF, Susmaras T, Caughlin BP, et al. White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain. 2007 Oct;130(Pt 10):2508-19.
7. Williams A, Piaton G, Aigrot MS, et al. Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain. 2007 Oct;130(Pt 10):2554-65.
8. Mandel SA, Sagi Y, Amit T. Rasagiline promotes regeneration of substantia nigra dopaminergic neurons in post-MPTP-induced Parkinsonism via activation of tyrosine kinase receptor signaling pathway. Neurochem Res. 2007 Oct;32(10):1694-9.
9. Holmberg E, Nordstrom T, Gross M, et al. Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules found in central nervous system injury. J Neurotrauma. 2006 Sep;23(9):1366-78.
10. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
11. Ke Y, Chi L, Xu R, et al. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells. 2006; 24(4): 1011-1019..
12. McLaren A. A scientist's view of the ethics of human embryonic stem cell research. Cell Stem Cell. 2007 Jun 7;1(1):23-6.
13. Ando T, Yujiri T, Nomiyama J, et al. Allogeneic peripheral blood stem cell transplantation from related donors mismatched at 2 HLA loci in the host-versus-graft direction. Tohoku J Exp Med. 2008 Feb;214(2):159-63.
14. Zhang SJ, Zhang H, Hou M, et alIs it possible to obtain "true endothelial progenitor cells" by in vitro culture of bone marrow mononuclear cells? Stem Cells Dev. 2007 Aug;16(4):683-90.
15. Mouiseddine M, Fran?ois S, Semont A, et al. Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol. 2007 Sep;80 Spec No 1:S49-55.
16. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
17. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
18. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Zhonghua Yi Xue Za Zhi. 2005 Jul 20; 85(27): 1883-1884.
19. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb;25(2):371-379
20. Lee MW, Choi J, Yang MS, et al. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2004; 320: 273-278.
21. Bauhofer A, Schwarting RK, K?ster M, et al. Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials. Inflamm Res. 2004 Dec;53(12):697-705.
22. Zhang Y, Adachi Y, Suzuki Y, et al. Synergistic effects of granulocyte-colony stimulating factor and macrophage-colony stimulating factor on recovery of donor hematopoietic cells in allogeneic bone marrow transplantation. Oncol Rep. 2006Aug;16(2):367-71.
23. Chen J, Larochelle A, Fricker S, Bridger G, Dunbar CE, Abkowitz JL. Mobilization as a preparative regimen for hematopoietic stem cell transplantation. Blood. 2006; 107(9): 3764-3771.
24. Robinson SN, Pisarev VM, Chavez JM, et al . Use of matrix metalloproteinase (MMP)-9 knockout mice demonstrates that MMP-9 activity is not absolutely required for G-CSF or Flt-3 ligand-induced hematopoietic progenitor cell mobilization or engraftment. Stem Cells. 2003; 21(4): 417-427.
25. Zvaifler NJ, Marinova-ML, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000; 2: 477-488.
26. Lazarus HM, Haynesworth SE, Gerson SL, et al. Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother. 1997; 6: 447-455.
27. Burt RK, Loh Y, Pearce W, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA. 2008 Feb 27;299(8): 925-36.
28. Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008 Feb 22;132(4):681-96.
29. Chan BP, Hui TY, Yeung CW, et al. Self-assembled collagen-human mesenchymal stem cell microspheres for regenerative medicine. Biomaterials. 2007; 28(31): 4652-4666.
30. Guo CA, Liu XG, Huo JZ, et al. Novel gene-modified-tissue engineering of cartilage using stable transforming growth factor-beta1-transfected mesenchymal stem cells grown on chitosan scaffolds. J Biosci Bioeng. 2007; 103(6): 547-556.
31. Tiina M, Jarmo L. Placenta—an alternative source of stem cells . Toxicology and Applied Pharmacology 2005; 207( 2): 544-549.
32. Porada CD, Zanjani ED, Almeida-Porad G. Adult mesenchymal stem cells: a pluripotent population with multiple applications. Curr Stem Cell Res Ther. 2006 Sep;1(3):365-9.
33. Pountos I, Corscadden D, Emery P, et al. Mesenchymal stem cell tissue engineering: techniques for isolation, expansion and application. Injury. 2007 Sep;38 Suppl4:S23-33.
34. David CC,Reiner C,CarlaM, et al. Rapid expansion of fecycling stem cells in cultrues of plastic-adheren cells from human bone marrow[J]. Proc Natl Aca SciUSA, 2000, 97(7): 3213-3218.
35. Heaney NB, Holyoake TL. Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol. 2007 Jun;25(2):66-75.
36. Spencer A, Jackson J, Baulch-Brown C. Enumeration of bone marrow 'homing' haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation. Bone Marrow Transplant. 2001 Dec;28(11):1019-22.
37. Roberts AW. G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors. 2005 Mar;23(1):33-41.
38. Vianello F, Dazzi F. Mesenchymal stem cells for graft-versus-host disease: a double edged sword? Leukemia. 2008 Mar;22(3):463-5. No abstract available.
39. Beyer NN, da Silva ML. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol, 2006; (174): 249-282.
40. Delorme B, Charbord P. Culture and characterization of human bone marrow mesenchymal stem cells. Methods Mol Med. 2007;140:67-81.
41.邓均,粟永萍.骨髓间充质干细胞可塑性研究.生理科学进展, 2007; 38(2): 133-135
42. Yang XS, Wu HX, Xiao B. Human mesenchymal stem cells differentiate into neuron-like cells and show SMN protein expression. Zhonghua Yi Xue Za Zhi, 2005, 85(16): 1125-1128.
43.邓均,艾国平,粟永萍等. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
44. Yim EK, Pang SW, Leong KW. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res. 2007 May 15;313(9):1820-1829.
45. Inoue K, Noda S, Ogonuki N, et al. Differential developmental ability of embryos cloned from tissue-specific stem cells. Stem Cells. 2007 May;25(5):1279-1285.
46. Satake K, Lou J, Lenke LG, et al. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine. 2004; 29(18): 1971-1979.
47. Qi X, Yang DL, Qi F, et al. Statistical analysis on 2213 inpatients with traffic injuries from January 2003 to September 2005 in Ningbo city. Chin J Traumatol. 2006 Aug;9(4):228-33.
48. Odebode TO, Ologe FE. Facial nerve palsy after head injury: Case incidence, causes, clinical profile and outcome. J Trauma. 2006 Aug;61(2):388-91.
49. Lee KS. Estimation of the incidence of head injury in Korea: an approximation based on national traffic accident statistics. J Korean Med Sci. 2001 Jun;16(3):342-6.
50. Itoh T, Satou T, Nishida S, et al. Immature and mature neurons coexist among glial scars after rat traumatic brain injury. Neurol Res. 2007 Oct;29(7):734-42.
51. Kovesdi E, Czeiter E, Tamas A, et al. Rescuing neurons and glia: is inhibition of apoptosis useful? Prog Brain Res. 2007;161:81-95.
52. Rink A,Fung KM, Trejanouski JQ,et al. Evidence of apoptosis cell death after experience traumatic brain injury in the rat. Am J Pathol, 1995; 147(6):1575-1589
53. Tashlykov V, Katz Y, Gazit V, et al. Apoptotic changes in the cortex and hippocampus following minimal brain trauma in mice. Brain Res. 2007 Jan 26;1130(1):197-205.
54. Morrison B, Cater HL, Benham CD, et al. An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures. J Neurosci Methods. 2006 Jan 30;150(2):192-201.
55. Fischer C, Mutschler V. Traumatic brain injuries in adults: from coma to wakefulness. Neurophysiological data. Ann Readapt Med Phys. 2002 Nov;45(8):448-55.
56. Mac Donald CL, Dikranian K, Bayly P, et al. Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci. 2007 Oct 31;27(44):11869-76.
57. Marmarou A, Montasser PD, Foda AE, et al. A new model of diffuse brain injury in rats [J]. J Neurosurg, 1994, 80: 291-300.
58. Bederson JB, Pitts LH, Tsuji M, et a1. Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination [J]. Stroke, 1986, 17(3):472-476.
59. Shapira Y, Lam AM, Eng CC, et a1. Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury [J]. Stroke, 1994, 25(8): 1637-1643.
60. Langlois JA, Rutland B W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):375-8.
61. Shindo T, Matsumoto Y, Wang Q, et al. Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury. J Med Invest. 2006 Feb;53(1-2):42-51.
62. Boockvar JA, Schouten J, Royo N, et al. Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery. 2005;56(1):163-71.
63. Hahn JY, Cho HJ, Kang HJ, et al. Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol. 2008 Mar 4;51(9):933-43.
64. Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007 Oct;25(10):2648-59.
65. Lévesque JP, Winkler IG, Larsen SR, et al. Mobilization of bone marrow-derived progenitors. Handb Exp Pharmacol. 2007;(180):33-6.
66. Li H, Fu X, Ouyang Y, et al. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res. 2006 Dec;326(3):725-36.
67. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Zhonghua Yi Xue Za Zhi. 2005 Jul 20; 85(27): 1883-1884.
68. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb;25(2):371-379.
69. Sun AN, Wu DP, Wang Y, et al. Clinical study on haploid HLA-matched hematop-oietic stem cell transplantation for treatment of malignant hematological disease [J]. Ai Zheng, 2006, 25(8): 1019-1022.
70. Frangoul H, Nemecek ER, Billheimer D, et al. A prospective study of G-CSF primed bone marrow as a stem-cell source for allogeneic bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium (PBMTC) study. Blood. 2007 Dec 15;110(13):4584-7.
71. Gomez RC, Pinto MA, Gonzalez BM. Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia[J]. Clin Transl Oncol, 2006, 8(10): 729-734.
72. Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26.
73. Tigue CC, McKoy JM, Evens AM, et al. Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant. 2007 Aug;40(3):185-92.
74. Von AS, Hartung T. Potential for immune reconstitution through G-CSF treatment of HIV patient s [J]. Arch Immunol Ther Exp (Warsz), 2002, 50(2): 111-120.
75. Marshall JC. The effects of granulocyte colony-stimulating factor in preclinical models of infection and acute inflammation. Shock. 2005 Dec;24 Suppl 1:120-9.
76. Lehrke S, Mazhari R, Durand DJ, et al. Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circ Res, 2006; 99(5): 553-560.
77. Sokolova IB, Fedotova OR, Zin'kova NN, et al. Effect of mesenchymal stem cell transplant- ation on cognitive functions in rats with ischemic stroke. Bull Exp Biol Med. 2006 Oct;142(4):511-4.
78. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects ofgranulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
79. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
80. Woei CS, Shinn ZL, Hui YB, et al. Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor Stimulated Stem Cells. Circulation. 2004, 28;110(13):1847-54.
81. UrdzíkováL, JendelováP, GlogarováK,et al. Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma. 2006 Sep;23(9):1379-91.
82. Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005 Aug;33(2):145-52.
83. Shyu WC, Lee YJ, Liu DD, et al. Homing genes, cell therapy and stroke. Front Biosci. 2006 Jan 1;11:899-907.
84. Obeyesekere MN, Berry RW, Spicer PP, et al. A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization into the peripheral blood. Cell Prolif. 2004 Aug;37(4):279-94.
85. Lee C, Evans CA, Spooncer E, et al. Generation of a conditionally immortalized myeloid progenitor cell line requiring the presence of both interleukin-3 and stem cell factor to survive and proliferate. Br J Haematol. 2003 Sep;122(6):985-95.
86. Nadri S, Soleimani M, Hosseni RH, et al. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol. 2007;51(8):723-9.
87. Meirelles Lda S, Nardi NB. Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br J Haematol. 2003 Nov;123(4):702-11.
88. Cho HJ, Kim TY, Cho HJ, et al. The effect of stem cell mobilization by granulocyte-colony stimulating factor on neointimal hyperplasia and endothelial healing after vascular injury with bare-metal versus paclitaxel-eluting stents. J Am Coll Cardiol. 2006 Jul 18;48(2):366-74.
89. Viswanathan A, Painter RG, Lanson NA et al. Functional expression of N-formyl peptide receptors in human bone marrow-derived mesenchymal stem cells. Stem Cells. 2007 May;25(5):1263-9.
90. Kimura A, Ohmori T, Ohkawa R, et al. Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells. 2007 Jan;25(1):115-24.
91. Zhao J, Moore AN, Redell JB, et al. Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci. 2007 Sep 19;27(38):10240-8.
92. Habgood MD, Bye N, Dziegielewska KM, et al. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci. 2007 Jan;25(1):231-8.
93. Burt D, Salvidio G, Tarabra E, et al. The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes. Am J Pathol. 2007 Dec;171(6):1789-99.
94. Ishida Y, Kimura A, Kondo T, et al. Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration. Am J Pathol. 2007 Mar;170(3):843-54.
95. Schmal H, Niemeyer P, Roesslein M, et al. Comparison of cellular functionality of human mesenchymal stromal cells and PBMC. Cytotherapy. 2007;9(1):69-79.
96. Goings GE, Sahni V, Szele FG. Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 2004; 96(2): 213-226
97. Czarnowska E, Gajerska-DM, Ku?mierski K, et al. Expression of SDF-1-CXCR4 axis and an anti-remodelling effectiveness of foetal-liver stem cell transplantation in the infarcted rat heart. J Physiol Pharmacol. 2007 Dec;58(4):729-44.
98. Nagasawa T. The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche. Adv Exp Med Biol. 2007;602:69-75.
99. Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008 Jan;15(1):49-58.
100.Ratajczak MZ, Zuba-Surma E, Kucia M, et al. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006 Nov;20(11):1915-24.
101.Bhakta S, Hong P, Koc O. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med. 2006 Jan-Mar;7(1):19-24.
102.T?gel F, Isaac J, Hu Z, et al. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005 May; 67(5): 1772-84.
103.Lobanov AV, Uzdenski? AB. Neutrophin NGF protects glial cells, but not stretch receptor neurons of the crayfish Astacus astacus from photooxidative stress. Zh Evol Biokhim Fiziol. 2007 Sep-Oct;43(5):448-9.
104.Zhou HL, Yang HJ, Li YM, et al. Changes in Glial Cell Line-derived Neurotrophic Factor Expression in the Rostral and Caudal Stumps of the Transected Adult Rat Spinal Cord. Neurochem Res. 2008 May;33(5):927-37.
105.Wei D, Jin Z, J?rlebark L, et al. Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro. Dev Neurobiol. 2007 Jan;67(1):108-22.
106.Steinmetz CC, Buard I, Claudepierre T, et al. Regional variations in the glial influence on synapse development in the mouse CNS. J Physiol. 2006 Nov 15;577(Pt 1):249-61.
1. Burgess A, Metcalf D. Characterization of a serum factor stimulating the differentia- tion of myelomonocytic leukemia cells[J] . Int J Cancer, 1980, 26 (5): 647-651.
2. Kuderer NM, Dale DC, Crawford J, et al. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. 2007 Jul 20; 25(21): 3158-3167.
3. Donini M, Fontana S, Savoldi G, et al. G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007 Jun 1;109(11):4716-4723.
4. Kurdi M, Booz GW. G-CSF-based stem cell therapy for the heart-unresolved issues part A: paracrine actions, mobilization, and delivery. Congest Heart Fail. 2007 Jul-Aug; 13(4): 221-227.
5. Sehara Y, Hayashi T, Deguchi K, et al. Potentiation of neurogenesis and angiogenesis by G-CSF after focal cerebral ischemia in rats. Brain Res. 2007 Jun 2; 1151:142-149.
6. Piscaglia AC, Shupe TD, Oh SH, et al. Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats. Gastroenterology. 2007 Aug; 133(2): 619-631.
7. Boneberg EM ,Hartung T. Molecular aspects of anti-inflammatory action of G-CSF[J ] . Inflamm Res, 2002, 51 (3): 119-128.
8. Hoglund M. Glycosylated and non-glycosylated recombinant man granulocyte colony-stimulating factor ( rhG-CSF)-what difference ? [J] . Med Oncol, 1998, 15 (4): 229-233.
9. Layton JE, Hall NE. The interaction of G-CSF with its receptor [J]. Front Biosci, 2006, 1 (11): 3181-3189.
10. Sun AN, Wu DP, Wang Y, et al. Clinical study on haploid HLA-matched hematop- oietic stem cell transplantation for treatment of malignant hematological disease [J]. Ai Zheng, 2006, 25(8): 1019-1022.
11. Gomez RC, Pinto MA, Gonzalez BM. Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia[J]. Clin Transl Oncol, 2006, 8(10): 729-734.
12. Von AS, Hartung T. Potential for immune reconstitution through G-CSF treatment of HIV patient s [J]. Arch Immunol Ther Exp (Warsz), 2002, 50(2): 111-120.
13. Murry CE, Wiseman RW, Schwartz SM, et al. Skeleta myoblast trans-plantation for repair of myocardial necrosis [J]. J Clin Invest, 1996, 98: 2512-2523.
14. Kajstura J, LeriA, Finato N, et al. Myocyte p roliferation in end-stage cardiac failure in humans [J]. Proc Natl Acad Sci USA, 1998, 2195(15): 8801-8805.
15. Beltermi AP, Urbanek, KajsturaJ, et al. Evidence that human cardiacmyocytes divide aftermyocardial infarction[J]. N Engl JMed, 2001, 344(23): 1750-1774.
16. Ieishi K, Nomura M, Kawano T, et al. The effect of G-CSF in a myocardial ischemia reperfusion model rat. J Med Invest. 2007 Feb; 54(1-2): 177-183.
17. Muller P, Pfeiffer P, Koglin J, et al. Cardiomyocytes of noncardiac origin in myocardial biop sies of human transp lanted hearts [J]. Circulation, 2002, 106 (1): 31-35.
18. Bittira B, Shum TD, Khaldi A, et al. Mobilization and homing of bone marrow stromal cells in myocardial infarction[J]. Eur J Cardio - thorac Surg, 2003, 24(3): 393-398.
19. CiullaM M, Lazzari L, Pacchiana R, et al. Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury [J]. Haematologica, 2003, 88 (6): 614-621.
20. Bittira B, Shum T im D, Khaldi A. Mobilization and hom ing of bone marrow stromalcells in myocardial infarction. Euro J Cardio Tho rac Surg,2003, 24:393-398.
21. KocherA A, SchusterM D, Szabo MJ, et al. Neovascularization of ischemia myocardium by human bone marrow derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and imp roves cardiac function[J]. N at Med, 2001, 7: 430-436.
22. Assmus B, Schach V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction ( TOPCARE AM I)[J]. Circulation, 2002, 106: 3009-3017.
23. Fuch S, Baffou R, Zhou YF, et al. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia[J]. JACC, 2001, 37: 1726-1732.
24. Stauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans[J]. Circulation, 2002, 106: 1913-1918.
25. Wang JS, Shum TD, Chedrawy E, et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications [J]. J Tho rac Cardiovasc Surg, 2001, 122: 699-705.
26. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival[J]. P roc N atl A cad Sci, 2001, 98: 10344-10349.
27. Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell, 2002, 109(5): 625-637.
28. Deten A, Volz HC, BriestW, et al. Cardiac cytokineexp ression is up regulated in the acute phase after myocardial infarction: experimental study in rats[J]. Cardiovasc Res, 2002, 55(2): 329-340.
29. Pillarisetti K, Gupta SK. Cloning and relative expression analysis of rat stromal cell derived factor-1 ( SDF-1) , 1: SDF-1-mRNA is selectively induced in rat model of myocardial infarction [J]. Inflammation, 2001, 25(5) : 293-300.
30. Peled A, KolletO, Ponomaryov T, et al. The chemokine SDF-1 activates the integrins LFA-1,VLA-4, and VLA-5 on immature human CD34+ cells: role in transendothelial/stromal migration and engraftment of NOD /SCID mice[J]. Blood, 2000, 95(11): 3289-3296.
31. Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 onstem-cell homing and tissue regeneration in Ischaemic cardiomyopathy[J]. Lancet, 2003, 362(9385): 697-703.
32. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infracted heart, improving function and survival[J]. Proc NatlAcad Sci, 2001, 98 (18): 10344-10349.
33. Miki T, Sakamoto J, Nakano A, et al. Mobilization of bone marrow cells by G-CSF /M-CSF improves ventricular function in the heart undergoing post-infarct remodeling [J]. Circulation, 2002, 106: 15.
34. Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by granulocyte macrophage colony-stimulating factor in patients with coronary artery disease a randomized, double-blind, place bo-controlled study[J]. Circulation, 2001, 104(17): 2012-2017.
35. Kuethe F, Figulla HR, VothM, et al. Mobilization of stem cells by granulocyte colony-stimulating factor for there generation of myocardial tissue after myocardial infarction [J]. Dtsch Med Wochenschr, 2004, 129(9): 424-428.
36. Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improve damaged heart function [J]. Circulation, 1999, 100(19 supp l): 247-256.
37. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium[J]. Nature, 2001, 410(6829): 710-715.
38. Li L, Takemura G, Li Y, et al. Granulocyte colony-stimulating factor improves left ventricular function of doxorubicin-induced cardiomyopathy. Lab Invest. 2007 May; 87(5): 440-455.
39. Kocher AA, SchusterM D, SzabolcsM J, et al. Neovascularization of ischemicmyo- cardium by human bone marrow derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. NatMed, 2001, 7 (4): 430-436.
40. Gould E, Reeves AJ, Graziano MS, et al. Neurogenesis in the neocortex of adult primates. Science, 1999, 286: 548-552.
41. Zhang RL, Zhang ZG, Zhang L, et al. Proliferation and differentiation of progenitorcells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience, 2001, 105: 33-41.
42. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
43. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bonemarrow cells repair the infarcted heart, imp roving function and survival. Proc Natl Acad Sci USA, 2001, 98: 10344-10349.
44. Six I, Gasan G, Mura E, et al. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. Eur J Pharmacol, 2003, 458: 327-328.
45. Corti S, Locatelli F, Strazzer S, et al. Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment. Exp Neurol, 2002, 177: 443-452.
46. Gu W, Brannst om T, Wester P. Cortical neurogenesis in adult rat safter reversible photothrombotic stroke [J]. J Cereb Blood Flow Metab, 2000 ,20(8):1166-1173.
47. Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice[J]. Nature, 2000, 405(6789): 951-955.
48. Abe K. Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury [J]. J Cereb Blood Flow Metab, 2000, 20(10): 1393-1408.
49. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neurogenesis[J]. J Clin Invest, 2005, 115(8): 2083-2098.
50. Mahmood A, Lu D, Chopp M. Intravenous administ ration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury [J]. J Neurotrauma, 2004, 21(1):33-39.
51.邓均,艾国平,粟永萍. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
52.邓均,艾国平,粟永萍. G-CSF动员循环间充质干细胞及其对颅脑损伤修复的可行性分析.第三军医大学学报. 2007; 29(12): 1131-1134.
53. Hintzen RQ, Voormolen J, Sonneveld P, et al. Glioblastoma causing granulocytosis by secretion of granulocyte colony-stimulating factor[J]. Neurology, 2000, 54 (1): 259-261.
54. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stoke, 2003, 34(3): 745-751.
55. Da SN, Meyer MS, Menot ML, et al. G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8 ;21)translocation: basis for potential therapeutic efficacy[J]. Cytokines Cell Mol Ther, 1997, 3(2): 75-78.
56. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulo- cyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003, 34 (3): 745-751.
57. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteract sprogrammed cell death and drives neurogenesis. J Clin Invest [J]. Epub, 2005, 115(8): 2083-2098.
58. Mahmood A, Lu D, Chopp M. Intravenous administ ration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury[J]. J Neurot rauma, 2004, 21(1): 33-39.
59. Heard SO, Fink MP. Counter regulatory control of the acute inflammatory response: granulocyte colony-stimulating factor has anti-inflammatory properties[J]. Crit Care Med, 1999, 27: 1019-1021.
60. Heard SO, Fink MP, Gamelli RL, et al. Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute t rumatic brain injury or cerebral hemorrhage: the filgrastin study group[J]. Crit Care Med, 1998, 26:748-754.
61. Hebert JC, O’Reilly M, Gamelli RL. Protective effect of recombinant human gran- ulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice[J].Arch Surg, 1990, 125: 1075-1078.
62. Ihle JN. STATs: signal transducers and activators of transcription[J]. Cell, 1996, 84: 331-334.
63. Gibson CL, Jones NC, Prior MJ, et al. G-CSF suppresses edema formation and reduces interleukin-1βexpression after cerebral ischemia in mice[J]. J Neuropathol Exp Neurol, 2005, 64: 763-769.
64. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003, 34: 745-751.
65. Graham SH, Chen J, Clark RS. Bcl-2 family gene products in cerebral ischemia and traumatic brain injury[J]. J Neurotrauma, 2000, 17:831-841.
66. Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt[J]. Science, 1997, 275: 661-665.
67. Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis[J]. J Clin Invest, 2005, 115:2083-2098.
68. Chen J, Li Y, Katakowski M, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous ell proliferation after stroke in female rat[J]. J Neurosci Res, 2003, 73:778-786.
69. Krupinski J, Kaluza J, Kumar P, et al. Role of angiogenesis in patients with cerebral ischemic stroke[J]. Stroke, 1994, 25: 1794-1798.
70. Ca?izo MC, Lozano F, González-Porras JR, et al. Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. Cytotherapy. 2007;9(1):99-102.
71. Zhou B, Cao XC, Fang ZH, et al. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells. Acta Pharmacol Sin. 2007 Jan;28(1):89-97.
72. Cella G, Marchetti M, Vignoli A, et al. Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor. Leukemia. 2006 Aug;20(8):1430-4.
73. Takahashi T, Kalka C, Masuda H, et al. Ischemia and cytokine induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. [J]. Nat Med, 1999, 5(4): 434-438.
74. Lee ST, Chu K, Jung KH, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia [J]. Brain Res, 2005, 1058(1/2): 120- 128.
75. Shyu WC, Lin SZ, Yang HI, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells[J]. Circulation, 2004, 110:1847-1854.
76. Lataillade JJ, Clay D, Dupuy C, et al. Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival[J]. Blood, 2000, 95: 756-768.
77. Czarnowska E, Gajerska-DM, Ku?mierski K, et al. Expression of SDF-1-CXCR4 axisand an anti-remodelling effectiveness of foetal-liver stem cell transplantation in the infarcted rat heart. J Physiol Pharmacol. 2007 Dec;58(4):729-44.
78. Nagasawa T. The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche. Adv Exp Med Biol. 2007;602:69-75.
79. Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008 Jan;15(1):49-58.
80. Ratajczak MZ, Zuba-Surma E, Kucia M, et al. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006 Nov;20(11):1915-24.
81. Lachmund A, Gehrke D, Krieglstein K, et al. Trophic factors from chromaffin granules promote survival of peripheral and central nervous system neurous[J]. Neuroscience, 1994, 62: 361-370.
82. Cohen CS, Fraser SE. Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature, 1995, 378: 192-196.
83. Kang H, Schuman EM. Long-lasting neurotrophininduced enhancement of synaptic transmission in the adult hippocampus[J]. Scince, 1995, 267: 1658-1662.
84. Lindholm D. Neurotrophic factors and neuronal plasticity: is there a link[J]? Adv Neurol, 1997, 73: 1-6.
85. Wang Y, Lin SZ, Chiou AL, et al. Glial cell linederived neurotrophic factor protects against ischemiainduced injury in the cerebral cortex[J]. J Neurosci, 1997, 17: 4341-4348.
86. Li Y, Chen J, Chen XG, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery[J]. Neurology, 2002, 59: 514-523.
87. Stratos I, Rotter R, Eipel C, et al. Granulocyte-colony stimulating factor (G-CSF) enhances muscle proliferation and strength following skeletal muscle injury in rats. J Appl Physiol. 2007 Aug 23; [Epub ahead of print]
88. Dirsch O, Chi H, Gu YL, et al. Influence of stem cell mobilization and liver regeneration on hepatic parenchymal chimerism in the rat. Transplantation. 2006 Jun 27;81(12):1695-1699.
89. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver.Bull Exp Biol Med. 2005 Nov;140(5):644-647.
90. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res. 2006 Mar 15; 12(6): 1804-1812.
91.邓均,粟永萍.骨髓间充质干细胞可塑性研究.生理科学进展, 2007; 38(2): 133-135.
92. Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005 Jul 15;106(2):756-763.
1. Chan BP, Hui TY, Yeung CW, et al. Self-assembled collagen-human mesenchymal stem cell microspheres for regenerative medicine. Biomaterials. 2007; 28(31): 4652-4666.
2. Guo CA, Liu XG, Huo JZ, et al. Novel gene-modified-tissue engineering of cartilage using stable transforming growth factor-beta1-transfected mesenchymal stem cells grown on chitosan scaffolds. J Biosci Bioeng. 2007; 103(6): 547-556.
3. Tiina M, Jarmo L. Placenta—an alternative source of stem cells . Toxicology and Applied Pharmacology 2005; 207( 2): 544-549.
4. Amy C, Eric DL, Gregory M, et al. Fusion of neural stem cells in culture. Experimental Neurology 2006; 198( 1): 129-135.
5. David CC,Reiner C,CarlaM, et al. Rapid expansion of fecycling stem cells in cultrues of plastic-adheren cells from human bone marrow[J]. Proc Natl Aca SciUSA, 2000, 97(7): 3213-3218.
6. Pittenger F, Mackay A, Beck S, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411): 143-147.
7. Bruder SP, Jaiswal N, Haynesworth SE, et al. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subculativation and following cryopreser-vation[J].J Cell Biochem, 1997, 64(2): 278-294.
8. Lennon DP, Haynesworth SE, Young RG, et al. A chemically defined medium supprots in vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem cells[J]. Exp cell Res, 1995, 219(1): 211-222.
9. Conget PA, Minguell JJ. Phenotypical and functional properties of huamn bone marrow mesenchymal progenitor cells[J]. J Cell Physiol, 1999, 181(1): 67-73.
10.Tsai MS, Hwang SM, Tsai YL,et al. Clonal Amniotic Fluid-Derived Stem Cells Express Characteristics of Both Mesenchymal and Neural Stem Cells[J]. Biol Reprod, 2006, 74(10): 545-551.
11.Shih DT, Lee DC, Chen SC, et al. Isolation and Characterization of Neurogenic Mesenchymal Stem Cells in Human Scalp Tissue[J]. Stem Cells, 2005, 23(7):1012-1020.
12.Okamoto T, Aoyama T, Nakayama T, et al. Clonal heterogeneity in differenti- ation potential of immortalized human mesenchymal stem cells[J]. Biochem Biophys Res. Commun. 2002, 295(2): 354-361.
13.Muraglia A, Cancedda R, Quarto R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model[J]. J Cell Sci, 2000, 113(7): 1161-1166.
14.Conget PA, Mingguell JJ. Phenotypical and functional propertyes of human bone marrow mesenchymal progenitor cells[J] . J Cell Physiol, 1999, 181(1): 67-73.
15.Pittingger MF, Mackaya M, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J] . Science, 1999, 284(5411): 143-147.
16.Bruder SP, Ricalton NS, Boynton RE, et al. Mesenchymal stem cell surface antigen SB - 10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation[J] . J Bine Miner Res, 1998, 13(3): 655- 663.
17.Martinez C, Hofmann TJ, Marino R, et al. Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood. 2007 May 15; 109(10): 4245-4248.
18.Assia D, Geraldine LP, David JH, et al. Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells 2006; 10(9): 1634-1646.
19.Richardson LE, Dudhia J, Clegg PD, et al. Stem cells in veterinary medicine - attempts at regenerating equine tendon after injury. Trends Biotechnol. 2007 Aug 8; [Epub ahead of print]
20.Velloso CP, Simon A, Brockes JP. Mammalian postmitotic nuclei reenter the cell cycle after serum stimulation in new t/mouse hybrid myotubes. CurrBiol, 2001, 11(11): 855-858.
21.Kadiyala S, Young RG, Thide MA. Culture expanded ecanine mesenchymal stem cells possess osteochon drogenic potenial in vivo and in vitro[J].Cell Transplant,1997,6: 123-134.
22.Weike Si, Quan Kang, Hue HL, et al. CCN1/Cyr61 Is Regulated by the Canonical Wnt Signal and Plays an Important Role in Wnt3A-Induced Osteoblast Differentiation ofMesenchymal Stem Cells[J]. Mol.Cell.Biol., 2006, 26(8): 2955 - 2964.
23.Leonard JF, Patricia AZ, Chen Li, et al. Differential Expression Profiling of Membrane Proteins by Quantitative Proteomics in a Human Mesenchymal Stem Cell Line Undergoing Osteoblast Differentiation[J]. Stem Cells, 2005, 23(10): 1367-1377.
24.Angele P, Kajat R, Nerlich M, et al. Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin compostte sponge[J]. Tissue Eng, 1999, 5(6): 545-554.
25.Majumdar MK, Valeerit B, Pduso DP, et al. Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells[J]. J Cell Physiol, 2000, 185(1): 98-106.
26.Yonggang Pang, Pengcheng Cui, Wenxian Chen, et al. Quantitative Study of Tissue- Engineered Cartilage With Human Bone Marrow Mesenchymal Stem Cells[J]. Arch Facial Plast Surg, 2005,7(1): 7-11.
27.WakitaniS, SaitoT, CaplanAI, et al. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5 azacytidine[J]. Muscle Nerve, 1995, 18(12): 1417-1426.
28.Wakitania S, Satio T, Caplan AL. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J]. Muscle Nervd, 1995, 18(12): 1417-1426.
29.Ferrari G, Cusella DE, Angelis G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors[J]. Science, 1998, 279(5356): 1528-1530.
30.Wang JS, Shum T, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty feasibility and potential clinical advantages[J]. J Thorac Careiovasc Surg, 2000, 120(5): 999-1005.
31.Wangde Dai, Sharon LH, Bradley JM, et al. Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium: Short- and Long-Term Effects[J]. Circulation, 2005, 112(5): 214-223.
32.邓均,艾国平,粟永萍. C3H10T1/2细胞向神经元诱导分化的方法研究.中国修复重建外科杂志. 2007; 21(6): 638-641.
33.Yang XS, Wu HX, Xiao B. Human mesenchymal stem cells differentiate into neuron-like cells and show SMN protein expression. Zhonghua Yi Xue Za Zhi, 2005,85(16): 1125-1128.
34.Yim EK, Pang SW, Leong KW. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res. 2007 May 15;313(9):1820-1829.
35.Inoue K, Noda S, Ogonuki N, et al. Differential developmental ability of embryos cloned from tissue-specific stem cells. Stem Cells. 2007 May;25(5):1279-1285.
36.Den YB, Yuan QT, Liu XG, et al. Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons. Chin Med J (Engl), 2005, 118(18): 1533-1541.
37.Cho KJ, Trzaska KA, Greco SJ, et al. Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha. Stem Cells, 2005, 23(3): 383-391.
38.Kopen GC, Prockop DJ, Phinney DG, el at. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proc Natl Acad Sci,1999, 96(19): 10711-10716.
39.Brazelton TR, RossiFM, Keshet GL, et al. From marrow to brain: expression of neuronal phenotypes in adult mice[J]. Science, 2000, 290(5497): 1775-1779.
40.Chen J,Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats[J]. Stroke, 2001, 32(4): 1005-1011.
41.Bae JS, Furuya S, Shinoda Y, et al. Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice. Hum Gene Ther, 2005, 16(8): 1006-1011.
42.Zhang WW, Guo ZK. Problematic issues in clinical trials of mesenchymal stem cells and unraveling strategies-review. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):901-904.
43.Oh SH, Miyazaki M, Kouchi H, et al. Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro[J]. Biochem Biophys Res Com, 2000, 279(2):500-504.
44.Hong SH, Gang EJ, Jeong JA, et al. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem BiophysRes Commun, 2005, 330(4): 1153-1161.
45.Theise ND, Badves, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation[J]. Hepatology, 2000, 31(1): 235-240.
46.Wang JS, Shunrtim D, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages[J]. J Thora Cardiova Surg, 2000, 120(3): 999-1006.
47.Terai S, Sakaida I, Yamamoto N, et al. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes[J]. J Biochem, 2003, 134(4):551-558.
48.Yamamoto N, Terai S, Ohata S, et al. A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8,is useful for cell therapy to repair damaged liver[J]. Biochem Biophys Res Com, 2004, 313(4): 1110-1118.
49.Marina M, Barbara I, Carla Z, et al. Mesenchymal Stem Cells Are Renotropic, Helping to Repair the Kidney and Improve Function in Acute Renal Failure[J]. J Am Soc Nephrol. 2004, 15(7): 1794-1804.
50.Mauricio R, Jianguo X, Charles R, et al. Bone Marrow–Derived Mesenchymal Stem Cells in Repair of the Injured Lung. Am J Respir Cell Mol Biol, 2005, 33(2): 145-152.
51.Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007 Oct 4;449(7162):557-63.
52.Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells. 2007 Nov;25(11):2896-902. Epub 2007 Sep 27.
53.Chen XD, Dusevich V, Feng JQ, et al. Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res. 2007 Dec;22(12):1943-56.
54.Lin S, Rocky ST. Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow. FASEB J 2004; 10(4): 1096-1100.
55.Orkin SH, Zon L I. Hematopoiesis and stem cells : plasticity versus developmental heterogeneity. Nat Immunol 2002; 3(2): 323-328.
56.Rubio D, Garcia S, Paz MF, et al. Molecular characterization of spontaneousmesenchymal stem cell transformation. PLoS ONE. 2008 Jan 2;3(1):e1398.
57.Roubelakis MG, Pappa KI, Bitsika V, et al. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev. 2007 Dec;16(6):931-52.
58.Naujokat C, Sari? T. Concise review: role and function of the ubiquitin-proteasome system in mammalian stem and progenitor cells. Stem Cells. 2007 Oct;25(10):2408-18.
59.Maya S, Jennifer C, Jayme S, et al. Cell-Cell Fusion Induced by the Avian Reovirus Membrane Fusion Protein Is Regulated by Protein Degradation. J. Virol 2004; 78(11): 5996-6004.
60.Oliveri RS. Epigenetic dedifferentiation of somatic cells into pluripotency: cellular alchemy in the age of regenerative medicine? Regen Med. 2007 Sep;2(5):795-816.
61.Paulis M, Bensi M, Orioli D, et al. Transfer of a human chromosomal vector from a hamster cell line to a mouse embryonic stem cell line. Stem Cells. 2007 Oct;25(10):2543-50.
62.Nunes VA, Cava?ana N, Canovas M, et al. Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro only after exposure to in vivo muscle environment. Biol Cell. 2007 Apr;99(4):185-96.
63.Ying QL, Nichols J, Evans EP, et al. Changing potency by spontaneous fusion. Nature, 2002 , 416 (6880): 485-487.
64.Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002, 416(6880): 542-545.
65.Nichols J, Zevnik B, Anastassiadis K ,et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 1998, 95(3): 379-391.
66.Lysdahl H, Gabrielsen A, Minger SL, et al. Derivation and characterization of four new human embryonic stem cell lines: the Danish experience. Reprod Biomed Online. 2006 Jan;12(1):119-26.
67.Gibson TC, Pei Y, Quebedeaux TM, et al. Mitochondrial DNA deletions in primate embryonic and adult stem cells. Reprod Biomed Online. 2006 Jan;12(1):101-6.
68.Park YB, Kim YY, Oh SK, et al. Alterations of proliferative and differentiationpotentials of human embryonic stem cells during long-term culture. Exp Mol Med. 2008 Feb 29;40(1):98-108.
69.Jiang Y, Jahagirdar B, Reinhardt RL, et al. Pluripotecy of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418: 41-49.
70.Zipori D. The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther. 2006 Jan;1(1):95-102.
71.Siebert S, Anton-Erxleben F, Bosch TC. Cell type complexity in the basal metazoan Hydra is maintained by both stem cell based mechanisms and transdifferentiation. Dev Biol. 2008 Jan 1;313(1):13-24.
72.Clarke AR, Meniel V. The intestinal stem cell niche studied through conditional transgenesis. Ernst Schering Found Symp Proc. 2006;5:99-108.
73.Chen Y, Shao JZ, Xiang LX, et al. Mesenchymal stem cells: A promising candidate in regenerative medicine. Int J Biochem Cell Biol. 2008;40(5):815-20.
74.Ferrari M, Corradi A, Lazzaretti M, et al. Adult stem cells: perspectives for therapeutic applications. Vet Res Commun. 2007 Aug;31 Suppl 1:1-8.
1. Beschorner R, Dietz K, Schauer N, et al. Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol Histopathol, 2007; 22(5): 515-526.
2. Rink A, Fung KM, Trejanouski JQ, et al. Evidence of apoptosis cell death after experience traumatic brain injury in the rat. Am J Pathol, 1995; 147(6): 1575-1589
3. Kornblum HI. Introduction to neural stem cells. Stroke, 2007; 38(2): 810-816.
4. Ke Y, Chi L, Xu R, et al. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells. 2006; 24(4): 1011-1019.
5. Satake K, Lou J, Lenke LG, et al. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine. 2004; 29(18): 1971-1979.
6. Cheng TM, Shi CM, Su YP. Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Chinese Medical Journal. 2005 Jul 20; 85(27): 1883-1884.
7. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb; 25(2):371-379.
8. Gutierrez-RM, Reyes-ME, Mayani H, ea al. Characterization of the adherent cells developed in Dexter-type long-term cultures from human umbilical cord blood. Stem Cells. 2000; 18: 46-52.
9. Lee MW, Choi J, Yang MS, et al. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2004; 320: 273-278.
10. Zvaifler NJ, Marinova-ML, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000; 2: 477-488..
11. Wu GD, Nolta JA, Jin YS, et al. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation. 2003; 75: 679-685.
12. Lazarus HM, Haynesworth SE, Gerson SL, et al. Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother. 1997; 6: 447-455.
13. Wexler SA, Donaldson C, Denning KP, et al. Adult bone marrow is a rich source of human mesenchymal’stem’cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003; 121: 368-374.
14. Chen J, Larochelle A, Fricker S, Bridger G, Dunbar CE, Abkowitz JL. Mobilization as a preparative regimen for hematopoietic stem cell transplantation. Blood. 2006; 107(9): 3764-3771.
15. Robinson SN, Pisarev VM, Chavez JM, et al . Use of matrix metalloproteinase (MMP)-9 knockout mice demonstrates that MMP-9 activity is not absolutely required for G-CSF or Flt-3 ligand-induced hematopoietic progenitor cell mobilization or engraftment. Stem Cells. 2003; 21(4): 417-427.
16. Sotnikova NV, Stavrova LA, Gur'antseva LA, et al. Mechanisms of the effects ofgranulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med, 2005; 140(5): 644-647.
17. Lehrke S, Mazhari R, Durand DJ, et al. Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circ Res, 2006; 99(5): 553-560.
18. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res, 2006; 12(6): 1804-1812.
19. Marmarou A, Montasser PD, Foda AE, et al. A new model of diffuse brain injury in rats [J]. J Neurosurg, 1994, 80: 291-300.
20. Bederson JB, Pitts LH, Tsuji M, et a1. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination [J]. Stroke, 1986, 17(3): 472-476.
21. Shapira Y, Lam AM, Eng CC, et a1. Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury [J]. Stroke, 1994, 25(8): 1637-1643.
22. Beyer NN, da Silva ML. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol, 2006; (174): 249-282.
23. Kassis I, Zangi L, Rivkin R, et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006; 37(10): 967-976.
24. Zhang Y, Liang JL, Wang S, et al. Autologous bone marrow stromal cell transplantation with application of granulocyte colony-stimulating factor improves rabbit cardiac performance after acute myocardial infarction. Journal of Southern Medical University. 2007; 27(1): 43-45.
25. Ozaki K, Sato K, Oh I, et al. Mechanisms of immunomodulation by mesenchymal stem cells. Int J Hematol. 2007 Jul; 86(1): 5-7.