BMSCs在皮肤创伤修复中的作用
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
皮肤是人体面积最大的器官,也是机体自我更新速度最快的组织之一,它是机体免于脱水、损伤、感染的第一道防线,是维持内环境稳定和阻止微生物、化学物质等侵入的屏障。尽早覆盖创面,恢复皮肤的屏障功能,十分重要。常规的治疗方法采用自体皮肤或同种异体、异种皮肤的移植和人工替代物覆盖等,由于存在着供皮来源有限,同种异体、异种皮肤移植有免疫排斥反应或传染疾病的危险,人工皮肤费用昂贵等问题,常规方法难以满足临床应用的需要。因此,促进皮肤创伤修复已成为组织修复领域亟待解决的难题之一,研究皮肤创伤愈合修复具有重要的理论和实际意义。
     成体干细胞(adult stem cells,ASCs)是一类具有多向分化潜能的细胞群体,因其存在于各种组织及器官中,来源广泛,不涉及伦理问题,在临床救治中具有广泛的应用前景,已成为近年医学研究和应用的热点之一。目前,ASCs已经从大多数组织中被分离和鉴定,并且能够诱导分化为同一胚层或者不同胚层的细胞类型,显示了其多向分化的潜能。很多研究表明,将ASCs特别是骨髓间充质干细胞(Bone marrow-derived mesenchymal stem cells,BMSCs)应用于组织损伤修复,取得很好的效果。
     创伤形成的创面从根本上说是组织缺损,而干细胞独特的多向分化潜能、自我更新能力和增殖分化能力强的重要特性,正好满足皮肤修复的需要。大量实验研究发现,BMSCs在体内、体外可以分化为表皮细胞、成纤维细胞以及血管内皮细胞,这都为干细胞治疗皮肤创伤后缺损提供了理论支持。
     因此,针对皮肤创伤修复,本研究将BMSCs引入皮肤创伤后的创面治疗,围绕干细胞在创伤部位募集这一主题,明确BMSCs可以通过动员、募集作用参与创伤后组织修复,进一步作深入细致的研究,并初步探讨干细胞在创伤部位募集的机制,为临床治疗各种皮肤缺损提供了新的治疗思路。
     本研究首先对小鼠的BMSCs进行分离、培养,并对其进行诱导分化、鉴定,在此基础上观察了移植的BMSCs在皮肤创伤修复过程中募集现象,重点明确移植的BMSCs可以向创面募集,促进皮肤创伤的修复;同时,我们进一步探讨了其可能的机制,根据已知的趋化原理,采用基因转染的方法修饰BMSCs,促进BMSCs向创面的迁移,增加BMSCs向创面募集的数量,进一步提高BMSCs修复皮肤创伤的效果。
     主要结果和结论:
     1.本实验采用全骨髓贴壁法分离纯化BALB/C雄性小鼠的BMSCs,体外培养可大量扩增和传代,获得了体外培养扩增BMSCs的简单、稳定、高效的方法;通过实验鉴定及观察,BMSCs体外具有成骨、成脂肪诱导分化的潜能,已经符合种子细胞的基本条件,无论其“质和量”均能够满足进一步研究和应用的需要。
     2.本实验中采用Co60全身照射(照射剂量3.5Gy),使骨髓产生放射性损伤以造成受体骨髓灭活,为移植的BMSCs留出空间,减少了动物自体骨髓干细胞的影响,移植培养的BMSCs后,成功建立骨髓移植嵌合体模型,以模拟自体BMSCs的作用,满足实验需求。本实验骨髓移植嵌合体皮肤创伤动物模型的成功建立,为各种免疫功能不同小鼠放创复合伤模型建立提供了参考。
     3.本实验中,利用了三种不同细胞标记方式:CFDA-SE荧光标记、Y染色体标记、携带GFP基因的病毒载体转染标记BMSCs,通过给受体雌性BALB/C小鼠尾静脉注射来源于供体雄性BALB/C小鼠的标记BMSCs,分别利用组织切片后普通荧光显微镜观察,定量Real-timePCR检测创面组织中Y染色体的表达,以及冰冻切片后DAPI复染激光共聚焦显微镜观察,结果显示,无论从直观的现象观察,还是从创面组织Y染色体检测,都清楚地证实了BMSCs可以募集到创面,并参与了皮肤创伤的修复。
     4.创伤后免疫功能正常的BALB/C鼠创面的愈合时间为14.00±1.41d,而免疫功能缺陷的裸鼠、SCID鼠创面的愈合时间分别为17.16±1.17d和19.83±0.76d,与BALB/C鼠比较存在显著差异(P<0.01)。
     5.本实验通过RT-PCR检测创面组织中SDF-1的基因表达发现,创面愈合过程中BALB/C鼠SDF-1基因表达于伤后1d即有增高, 5d达峰值(P<0.01) ,然后逐渐下降,但仍明显高于对照组,14d创面基本愈合时接近对照组。而裸鼠、SCID鼠创面中SDF-1基因表达于伤后逐渐增高,所测时相点中伤后7d达峰值(P<0.01),与BALB/C鼠相比,SDF-1基因表达峰值延后,然后逐渐下降, 14d创面未愈合时,SDF-1基因表达仍高于对照组。本研究结果表明,SDF-1既是调节局部炎症的重要趋化因子,也是调节组织器官损伤修复的关键细胞因子。正常皮肤基础性表达SDF-1;创伤后,创面SDF-1表达增加,BMSCs募集到达创面,参与修复。另外机体的免疫功能也将影响BMSCs募集,从而影响创面愈合。这为临床上治疗各种创面,加速创面的尽早愈合提供了新的研究思路和方法。
     6.本实验成功地构建了CXCR4的腺病毒表达载体Adv-CXCR4,并转染BMSCs,尾静脉回输BMSCs检测创面组织中Y染色体的表达,结果显示:无论未转染Adv-CXCR4的BMSCs还是Adv-CXCR4转染的BMSCs移植,伤后1d,创面即检测到Y染色体,最高峰出现在伤后5d,持续明显表达14d以上;与未转染Adv-CXCR4的BMSCs相比,Adv-CXCR4转染的BMSCs移植后能更多地分布于BALB/C鼠的创面,二者相差显著(P<0.01)。同时,将Adv-CXCR4转染的BMSCs移植到BALB/C鼠的体内后,其创面平均愈合时间为12.46±1.17d,较移植未转染Adv-CXCR4的BMSCs的创面平均愈合时间14.00±1.41d,提前了1.5~2d。
As the biggest organ of the body and one of tissues with the fastest self-renewal, the skin is the first line of defense against dehydration, injury and infection,and plays an important role in maintaining homeostasis and preventing invasion of microorganisms and chemical substances. Therefore, it is critically important to recover barrier function after skin injury. Conventional therapies for skin injury included autogenous skin transplantation, auto-skin graft, hetero-skin graft as well as artificial surrogate coverage. However, because of limited resources of donor skin, auto-skin graft and hetero-skin graft may result in high cost and have risks of immunological rejection or disease infection, which adds difficulties to clinical application. Therefore, how to promote repair of skin wound is now one of tough problems and studies on repair of skin wound and wound healing are of theoretical and practical significance.
     Adult stem cells (ASCs) are a kind of cell colony with potential of multi-directional differentiation. In the meantime, ASCs can be obtained from all kinds of organs and tissues, without involvement in ethics problem, and has wide prospect of clinical application, which contributes to the fact that ASCs have been one of research hot spots in recent years. At present, ASCs have been separated from most tissues and identified, which shows that ASCs can be induced to differentiate into cell types at same or different embryonic layers, indicating its potential of multi-directional differentiation. Several studies reported that ASCs especially BMSCs could obtain satisfactory results for repair of tissue injury.
     Wound is tissue injury in itself. Stem cells have potential of multi-directional differentiation, self-renewal and good proliferation and differentiation and can satisfy requirement of skin repair. Large number of experiments found that BMSCs could in vivo and in vitro differentiate into epidermal cells, fibroblasts and vascular endothelial cells, which provides theoretical basis for skin wound repair with stem cells.
     The aim of the study was to ascertain whether BMSCs participated in repair of skin wound by means of mobilization and recruitment and preliminarily explore mechanism of stem cells recruiting at wound site so as to cater fresh treatment methods for all kinds of skin defects.
     In the study, BMSCs were first separated and cultured and then were induced to differentiate and identified. Recruitment of the transplanted BMSCs in repair of skin wound was observed to make sure whether the transplanted BMSCs could recruit towards wound to facilitate repair of skin wound. Meanwhile, the possible mechanism was further explored. Based current chemotaxis theory, BMSCs were modified by means of gene transfection to promote their migration to the wound skin and further boost effect of BMSCs in repair of skin wound.
     Main results and conclusions are as follows:
     1.We used variability adherence method for separation and purification of BMSCs from male BALB/C mice and found that in vitro culture could obtain large quantity of amplification and passages, which contributes to a simple, stable and effective method for in vitor culture and amplification of BMSCs. Experimental assessment and investigation showed that in vitro BMSCs had potential of inducing osteogenesis and adipogenesis, which accorded with pacing factor of seed cells and could meet demand of further studies.
     2.Systemic irradiation with Co60 (irradiation dose at 3.5Gy) was used in this study to induce radiation damage of bone marrow in order to inactivate host bone marrow, which may keep space for transplanted BMSCs and reduce influence of autogeneic bone marrow stem cells. After transplantation of cultured BMSCs, a bone marrow transplantation chimera model was successfully established to simulate function of autogeneic BMSCs, which caters reference for establishment of combined injury model of mice with different immune function.
     3.The study involved three kinds of cell labeling methods, ie, CFDA-SE fluorescence labeling, Y chromosomal marker and BMSCs labeling with adenovirus vector carrying GFP gene. After the labeled BMSCs from male BALB/C mice were injected into female BALB/C mice via vena caudalis, fluorescence microscope was used detect the labeled BMSCs and real-time PCR were employed to detect expression of Y chromosome in wound tissues after histological section; DAPI counterstain confocal microscopy was used detect the labeled BMSCs in wound tissues after frozen section. The results could clearly proved that BMSCs could be recruited on the wound and participate in repair of skin wound.
     4.The wound healing time for BALB/C mice with normal immune function after injury was (14.00±1.41) days, while that for nude mice and SCID mice with immune defects were (17.16±1.17) days and (19.83±0.76) days respectively, with statistical difference compared with BALB/C mice (P<0.01).
     5.Fluorescent quantitation RT-PCR was used to detect gene expression of SDF-1 in wound tissues, which showed that gene expression of SDF-1 was elevated in BALB/C mice at day 1 after injury and reached peak at day 5 (P<0.01). Gene expression of SDF-1 was then gradually decreased (but still remained higher than control group) and reached similar level to control group on primary wound healing at day 14. Gene expression of SDF-1in skin wound of nude mice and SCID mice was gradually increased after injury and reached peak at day 7 after injury (P<0.01), which was delayed compared with BALB/C mice. Gene expression of SDF-1was then gradually decreased and maintained at higher level than control group before wound healing at day 14. The results indicated that SDF-1 is either important chemotatic factor regulating regional inflammation or key cytokine regulating repair of tissue or organ injury. SDF-1 is expressed in normal skins. After skin wound, expression of SDF-1 is increased, when BMSCs are recruited on the wound for repair of the wound. In addition, immune function of the organism will affect recruitment of BMSCs and result in late wound healing, which provides novel method for clinical treatment of different kinds of wounds and promotion of wound healing.
     6.We successfully constructed adenovirus expression vector Adv-CXCR4 of CXCR4. BMSCs were transfected and retransfused via vena caudalis to detect expression of chromosome Y in wound skin tissues, which showed that chromosome Y was detected in wound skin tissues at day 1 after injury either for BMSCs free from Adv-CXCR4 tranfection or transplanted BMSCs transfected with Adv-CXCR4. The expression peak emerged at day 5, which lasted for over 14 days. In the meantime, compared with BMSCs free from Adv-CXCR4 transfection, transplanted BMSCs transfected with Adv-CXCR4 could distribute on the wound of BALB/C mice, with statistical difference (P<0.01). After BMSCs transfected with Adv-CXCR4 were transplanted into BALB/C mice, the wound healing time were (12.46±1.17) days, with 1.5~2 days shorter than (14.00±1.41) days for skin wound treated with transplantation of BMSCs free from transfection with Adv-CXCR4.
引文
1.景竹春,梁璐,韩忠朝.间充质干细胞在治疗皮肤缺损中的应用[J].国际生物医学工程杂志,2007,30(4):202-205.
    2.屈纪富,刘明华,等.干细胞与皮肤创伤愈合[J].世界急危重病医学杂志,2005,2(6):1011-1014.
    3. Schultz SS.Adult stem cell application in spine cord injury[J].Curr Drug Targets, 2005,6(1):63-73.
    4. Ma N,Stamm C,Kaminski A,Li W,et al.Human cord blood cells induce angiogenesis following myocardical infarction in NOD/scid-mice[J].Cardiovase Res,2005,66(1): 45-54.文亮,
    5.李高峰,刘浔阳,罗成群.干细胞与创面修复[J].医学临床研究,2003,20 (1):30-32.
    6.韩冰,付小兵,梁雪梅,等.烧伤大鼠血清诱导骨髓MSCs分化为表皮细胞和血管内皮细胞的实验研究[J] .解放军医学杂志, 2004,29: 652- 654.
    7.方利君,付小兵,王玉新,等.体外诱导骨髓MSCs分化为上皮细胞的研究[J].中华实验外科杂志,2004, 21: 171- 172.
    8. Krause DS, Theise ND, Collector MI, et al. Multi-organ multi-lineage engraftment by a single bone marrow-derived stem cell [J].Cell, 2001,105(3):369-377.
    9. Korbling M, Katz RL, Khanna A, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cell [J].N Engl J Med, 2002,346 (10):738-746.
    10. Badiavas EV, Abedi M, Butmarc J, et al. Participation of bone marnow derived cells in cutaneous wound healing[J]. J Cell Physiol, 2003,196(2):245-50.
    11. Abe R, Donnelly SC, Peng T, et al. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites[J]. J Immunol, 2001,166(12):7556-62.
    12.梁峰,王韫芳,南雪,等.体外诱导人骨髓MSCs定向血管内皮细胞分化[J] .中国医学科学院学报, 2005, 27: 665- 669.
    13. Silva GV, Litovsky S, Assad JA, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density,and improve heart function in a canine chronic ischemia model[ J] .Circulation, 2005, 111: 150- 156.
    14. Sekiya I,Larson BL, Smith JR,et al. Expansion of Human Adult Stem Cells from Bone Marrow Stroma: Conditions that Maximize the Yields of Early Progenitors and Evaluate Their Quality. Stem Cells,2002,20(6):530-541.
    1. Delorme B, Chateauvieux S, Charbord P. The concept of mesenchymal stem cells [J] . Regen Med, 2006, 1( 4) : 497- 509.
    2. Jackson L, Jones DR, Scotting P, et al. Adult mesenchymal stem cells: Differentiation potential and therapeutic applications [J] . J Postgrad Med, 2007, 53( 2) : 121- 127.
    3. ChoiYS ,Park SN ,Suh H .A dipose tissue engineering using m esenchymal stem cells attached to injectable PLG A spheres[J].Biomaterials,2005,26(29):5855-5863.
    4. Mauney JR,Volloch V,Kaplan DL. Matrix-mediated retention of adipogenicdifferentiation potentialby hum an adult bone m arrow–derived mesenchymal stem cells during ex vivo expansion[J].Biom aterials ,2005,26(31):6167-6175.
    5.庄淑波,刘毅.骨髓间充质干细胞在整形外科的应用前景[J].中国美容医学杂志,2006,3(15):347-349.
    6. Barry FP ,Murphy JM .Mesenchymal stem cell clinical applications and biological characterization[J].Biochem cell Biol,2004,36(4):568-584.
    7. Friedenstein A J,Chailakhyan RK ,Gerasimon UV . Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers[J].Cell Tissue Kinet,1987,20(3):263-267.
    8. Ferrari G,Cusella DG,Coletta M, et al. Muscle regeration by bone marrow derived myogenicprogenitors[J]. Science,1998,279 :152-1530.
    9. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al . Adult bone marrow stromal cell differentiate intoneural cells in vitro[J]. ExpNeuro,2000,164 : 247-256.
    10. Oh SH ,Miyazaki M,Kouchi H , et al . Hepatocyte growth factor induce differentiation of adult rat bone marrow cells into a heoatocyte lineage in vitro[J].Biochem Biophys Res Commun,2000 ,279:500-504.
    11. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J] . Exp Hematol, 1976, 4( 5) : 267-274.
    12. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells [J]. Science, 1999, 284(5411) : 143-147.
    13. Ohgushi H, Calplan AI. Stem cell techono logy and biocramics:from cell to gene engineering[J]. J Biomed Mater Res, 1999,48(6):913.
    14. Conget PA, Minguell JJ.Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells[J].J Cell Physiol.1999,181(1):67-73.,
    15. Kostenuik PJ , Halloran BP, Morey-Holton ER, et al. Skeletal unloading inhabits the in vitro proliferation and differentiation of rat osteoprogenitor cells[J]. Am J Physiol, 1997, 273 (6 P t 1):E1133.
    16. Lennen DP, Hayneswo rth SE, Young RG, et al. A chemically defined medium supports in vitro proliferation and maintains the osteochondral potential of rat marrow derived mesenchymal stem cells[J]. Exp Cell Res, 1995,219 (1):211.
    17. Maniatopoulos C, Sodek J , Melcher AH. Bone formation in vitro by stromal cellsobtained from bone marrow of young adult rats[J]. Cell T issue Res, 1988,254 (2):317.
    18. Izadpanah R, Joswig T, Tsien F, et al. Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesusmacaques [J] . Stem Cells Dev, 2005, 14( 4) : 440- 451.
    19. Tondreau T, Lagneaux L, Dejeneffe M, et al. Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection:phenotype, proliferation kinetics and differentiation potential [J] .Cytotherapy, 2004, 6( 4) : 372- 379.
    20. Alborxi A, Mac KG, Lackin CA, et al. Endochondral and intramembranous fetal bone development, osteoblastic cell proliferation and expression of alkaline phosphatase, m-twist, and histone H4[J] . Cranifac Genet Der Boil, 1996, 16(2) : 94-98.
    21. P rockop DJ. M arrow st romal cells as stem cells for nonhematopo iet ic t issues [J]. Science, 1997, 276: 71-75.
    22. Kitano Y, Radu A , Shabban A , et al. Selection, enrichment, and culture expansion of murine mesenchymal progenitor cells by retroviral transduction of cycling adherent bone marrow cells[J]. Exp Hemato l, 2000, 28(12) : 1460-1469.
    23. Deryugina EI, Muller-sieburg CE. Stromal cells in longterm cultures: keys to the elucidation of hematopoietic development[J]. Crit Rev Immunl, 1993, 13: 115.
    24.路艳蒙,傅文玉,朴英杰.大鼠间充质干细胞的培养[J].解剖学杂志, 2000, 23: 160.
    25. Tondreau T, Lagneaux L, Dejeneffe M, et al. Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection:phenotype, proliferation kinetics and differentiation potential [J] .Cytotherapy, 2004, 6( 4) : 372- 379.
    26. Izadpanah R, Joswig T, Tsien F, et al. Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesusmacaques [J] . Stem Cells Dev, 2005, 14( 4) : 440- 451.
    27. Baddoo M, Hill K, Wilkinson R, et al. Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection [J] . J Cell Biochem, 2003, 89( 6) : 1235- 1249.
    28. Tondreau T, Lagneaux L, Dejeneffe M, et al. Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection:phenotype, proliferation kinetics and differentiation potential [J] .Cytotherapy, 2004, 6( 4) : 372- 379.
    1. Francois S, Bensidhoum M, Mouiseddine M, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage[J]. Stem Cells, 2006,24: 1020-1029
    2. Shibata T, Naruse K, Kamiya H, et al. Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. [J]. Diabetes, 2008,57(11):3099-3107.
    3. Carvalho S, Cortez E, Stumbo AC,et al. Laminin expression during bone marrow mononuclear cell transplantation in hepatectomized rats[J].Cell Biol Int,2008,32(8): 1014-1018.
    4. Dorrell MI,Otani A,Aguilar E,et al.Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina[J].Blood, 2004,103(9):3420-3427.
    5. Palumbo R,Sampaolesi M,De Marchis F,et al.Extracellular HMGB1,a signal of tissue damage,induces mesoangioblast migration and proliferation.[J].J Cell Biol,2004, 164(3):441-449.
    6. VatsA, Bielby RC, Tolley NS, et al. Stem cells[J]. Lancet, 2005,366 (9485) : 592 - 602.
    7. Krause DS, Theise ND, Collector MI, et al.Multi-organ,multi-lineage engraftment by a single bone marrow-derived stem ce11.[J].Ce11,2001,105(3):369-377.
    8. Shiota M, Heike T, Haruyama M,et al.Isolation and characterization of bone marrow-derived mesenchymal progenitor cells with myogenic and neuronal properties.[J].Exp Cell Res,2007,313(5):1008-1023.
    9. Ratajczak MZ, Reca R, Wysoczynski M, et al. Modulation of the SDF-1-CXCR4 axis by the third complement component (C3)--implications for trafficking of CXCR4+ stem cells[J]. Exp Hematol,2006,34(8):986-995.
    10. Liu DD, Shyu WC, Lin SZ.Stem cell therapy in stroke: strategies in basic study and clinical application[J]. Acta Neurochir Suppl,2006,99:137-139.
    11. Shyu WC, Lee YJ, Liu DD,et al. Homing genes, cell therapy and stroke[J]. Front Biosci, 2006 ,11:899-907.
    12. Minguell JJ, Erices A, Congel P. Mesenchymal stem cells[J]. Exp Biol Med, 2001, 226 (6) : 507-520.
    13. Miura M, Miura Y, SonoyamaW, et al. Bone marrow derived mesenchymal stem cells for regenerative medicine in craniofacial region[J]. Oral Dis, 2006, 12 (6) : 514 - 522.
    14. Dumitriu IE, Mohr W, Kolowos W, et al. 5, 6-carboxyfluorescein diacetate succinimidyl ester labeled apoptotic and necrotic as well as detergent treated cells can be traced in composite cell samp les[J].Anal Biochem, 2001, 299 (2) : 247 - 252.
    15.陈蕾蕾,陈军浩,孙雪梅等.荧光染料CFSE作为细胞标记的特性研究[J].细胞与分子免疫学杂志,2004, 20(2):140-141.
    16.付霞霏,何援利,杨芳等.BrdU, CFSE和GFP标记大鼠间充质干细胞的比较[J].第四军医大学学报,2008, 29 (5):399-402.
    17.付霞霏何援利.大鼠间充质干细胞的体外分离培养及CFSE标记[J].解放军医学杂志,2007,32(5):464-466.
    18. Oostendorp RA, Audet J, Eaves CJ. High resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo[J]. Blood, 2000, 95 (3) : 855 -862.
    19. Burns TC, Ortiz Gonzalez XR, Gutierrez Perez M, et al. Thymidine analogs are transferred from p relabeled donor to host cells in the central nervous system after transp lantation: aword of caution[J]. Stem cells, 2006, 24 (4) : 1121-1127.
    20. Yahata T,Ando K,Sato T,et al. A highly sensitive strategy for SCID-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID micebone marrow[J]. Blood,2003,101(8): 2905-2913.
    21. Oostendorp RA, Audet J, Eaves CJ. High resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo[J]. Blood, 2000, 95 (3) : 855.
    22. Nordon RE, Ginsberg SS, Eaves CJ. High resolution cell division tracking demonstrates the FLt3-ligand dependence of human marrow CD34+CD38 cell production in vitro[J]. Br J Haematol, 1997, 98 (3) : 528.
    23. Hasbold J, Hodgkin PH. Flow cytometric cell divisiontracking using nuclei [J]. Cytometry, 2000, 40 (3) : 230.
    24. Summary.Great circulation of stem cell[J].Science,2001,294(5548):1785.
    25. Tokumasu F,Dvorak J.Development and application of quantum dots for immunocy- tochemistry of human erythrocytes [J]. J Microscopy ,2003, 211(pt3): 256-261.
    26. Neumann M,Gabel D.Simple Method for Reduction of Autofluorescence in Fluorescence Microscopy[J]. J Histochem- Cytochem,2002, 50(3:)437-439.
    27. Koetsier M, Lutgers H, Smit A. J ,etal. Skin autofluorescence for the risk assessment of chronic complications in diabetes: a broad excitation range is sufficient [J].Opt- Express,2009,17(2):509-519 .
    1. Rosu-Myles M, Bhatia M. SDF-1 enhances the expansion and maintenance of highly purified human hematopoietic progenitors[J].Hematol J,2003,4(2):137-145.
    2. MisaoY, Arai M, Ohno T, et al.Modification of post-myocardial infarction granulocyte-colony stimulating factor therapy with myelo-suppressives[J]. Circ J,2007,71(4):580-590.
    3. YJ, Ryu KH, Cho SJ,et al. Syngenic bone marrow cells restore hepatic function in carbon tetrachloride-induced mouse liver injury[J]. Stem Cells ,2006 ,15(5):687-695.
    4. ShibaY, Takahashi M, Yoshioka T, et al.M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4system[J]. Arterioscler Thromb Vasc Biol,2007,27(2):263-265.
    5. Backesjo CM, Li Y, Lindgren U, et al. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells[J]. J Bone Miner Res, 2006,21(7):993-1002.
    6. Shibata T, Naruse K, Kamiya H, et al. Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats[J]. Diabetes, 2008,57(11):3099-3107.
    7.刘晓,王建,卢光琇.细胞生长因子与创伤愈合[J].现代生物医学进展,2008,8(9): 1753-1755.
    8. Diegelmann RF,Evans MC.Wound healing: an overview of acute, fibrotic and delayed healing[J].Front Biosci,2004,9:283-289.
    9. Martin P. Wound heal-aiming for perfect skin regeneration. Science,1997,276(5309): 75-81.
    10. Shi C , Cheng T , Su Y, et al . Transplantation of dermal multipotent cells promotes survival and wound healing in rats with combined radiation and wound injury[J]. Radiat Res, 2004, 162(1): 56-63.
    11. Qu J , Cheng T , Shi C , et al . A study on the activity of fibroblast cells in connection with tissue recovery in the wounds of skin injury after Whole body irradiation[J]. J Radiat Res , 2004 , 45 : 341-344.
    12. Shi CM , Cheng TM, Su YP, et al . Transplantation of dermal multipotent cells promotes the hematopoietic recovery in sublethally irradiated rats[J]. J Radiat Res(Tokyo) , 2004, 45(1): 19-24.
    13.史春梦,程天民,屈纪富等.神经生长因子同时促进放创复合伤小鼠创面愈合和造血恢复的实验研究[J].中华放射医学与防护杂志,2002,22(3):161-162.
    14. Francois S, Bensidhoum M, Mouiseddine M, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage[J]. Stem Cells, 2006; 24: 1020-1029.
    15. Pablos JL, Amara A, Bouloc A,et al.Stromal-Cell Derived Factor Is Expressed by Dendritic Cells and Endothelium in Human Skin[J].Am J Pathol,1999,155(5): 1577-1586.
    16. Ceradini DJ,Kulkarni AR,Callaghan MJ,et al.Progenitor cell trafficking is regulated by hypoxic gradient s t hrough HIF-1 induction of SDF-1[J].Nat Med ,2004,10 (8) :858-864.
    17.张谊,曹川李世荣等.皮肤损伤后SDF-1分泌量的变化及其受体CXCR4在表皮组织中分布表达的实验研究[J].现代生物医学进展,2008,8(6):1061-1062.
    18. Ratajczak MZ, Reca R, Wysoczynski M, et al. Modulation of the SDF-1-CXCR4 axis by the third complement component (C3)--implications for trafficking of CXCR4+ stem cells[J]. Exp Hematol. 2006,34(8):986-995.
    19. Zong ZW, Cheng TM, Su YP,et al.Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal multipotent cells to sublethally irradiated bone marrow[J]. J Radiat Res (Tokyo),2006,47(3-4):287-293.
    20. Wang Y, Haider HKh, Ahmad N, et al. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts[J].J Mol Cell Cardiol,2006 ,41(3): 478-487.
    21. Lee SP, Youn SW, Cho HJ, et al. Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue[J]. Circulation, 2006 ,114(2):150-159.
    22. Kucia M, Wojakowski W, Reca R, et al.The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner[J]. Arch Immunol Ther Exp (Warsz), 2006,54(2):121-135.
    23. Gotoh A ,Reid S ,Miyazawa K,et al. SDF-1 suppresses cytokine-induced adhesion of human haemopoietic progenitor cells to immobilized fibronectin[J].Br J Haematol ,1999 ,106 (1) :171
    24. 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
    25. Yonezawa A,Hori T,Sakaida H, et al.SDF-1 has costimulatory effects on human T cells: possible involvement of MAPK (ERK2) activation[J]. Microbiol-Immunol,2000,44(2): 135-141.
    26. Ponte A L, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factorchemotactic activities[J]. Stem Cells, 2007,25(7):1737-1745.
    27. Nanki T,Lipsky PE.Cutting edge: stromal-cell derived factor-1is a co-stimulator for CD4′T cell activation[J].J Immunol ,2000,164 (10) :5010-5014.
    28. Yonezawa A,Hori T,Sakaida H, et al.SDF-1 has costimulatory effects on human T cells: possible involvement of MAPK (ERK2) activation[J].Microbiol-Immunol,2000,44(2): 135-141.
    29.冯帅南,黄宏,张波等.小鼠全层皮肤创伤愈合过程中基质细胞衍生因子-1及其受体CXCR4基因表达的研究[J].感染、炎症、修复,2008,9(3):142-145.
    30.宗兆文,程天民,冉新泽等.放创复合伤大鼠伤口液对真皮多能干细胞的趋化作用及其意义[J].中华放射医学与防护杂志,2005,25:104-106.
    31.宗兆文,程天民,冉新泽等.移植dMSCs向放创复合伤创面优势分布的机制研究[J]。中华放射医学与防护杂志,2006,26(4):313-316.
    1. Pasha Z,Wang Y ,Sheikh R,et al. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium [J]. Cardiovasc-Res, 2008 ,77(1): 134-142
    2. Petty JM,Sueblinvong V,Lenox CC,et al. Pulmonary stromal-derived factor-1 expression and effect on neutrophil recruitment during acute lung injury [J].J-Immunol, 2007, 178(12): 8148-8157.
    3. Shiba Y,Takahashi M,Yoshioka T,et al. M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system [J]. Arterioscler-Thromb-Vasc-Biol,2007 , 27(2): 283-289.
    4. Xu J,Mora A,Shim H,et al. Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis [J]. Am-J-Respir-Cell-Mol-Biol,2007 ,37(3): 291-299.
    5.宗兆文,程天民,冉新泽,等.放创复合伤大鼠伤口液对真皮多能干细胞的趋化作用及其意义[J].中华放射医学与防护杂志,2005,25:104-106.
    6.宗兆文,程天民,冉新泽,等.移植dMSCs向放创复合伤创面优势分布的机制研究[J]。中华放射医学与防护杂志,2006,26(4):313-316.
    7. Feng Y, Broder C C , Kennedy P E , et al. HIV-1 Entry co-factor : functional cDNA cloning of a seven-transmembrane,G protein coupled receptor [J].Science,1996, 272(5263) :872-827.
    8. Kahn J, Byk T, Jansson-Sjostrand L,et al.Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation[J]. Blood, 2004, 103( 8): 2942-2949.
    9. Brenner S, Whiting-Theobald N, Kawai T,et al.CXCR4-Transgene Expression Significantly Improves Marrow Engraftment of Cultured Hematopoietic Stem Cells[J]..Stem Cells, 2004, 22(7): 1128-1133.
    10. Lien CY,Chih-Yuan-Ho K,Lee OK,et al.Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells[J]. J-Bone-Miner-Res, 2009 , 24(5): 837-848.
    11. Zhang Y, Ou L,Cheng,Z, et al.Genetic modification of bone marrow mesenchymal stem cells with human CXCR4 gene and migration in vitro[J]. Sheng-Wu-Yi-Xue-Gong-Cheng-Xue-Za-Zhi. 2009,26(3): 595-600.
    12. Zong ZW,Xiang Q, Cheng TM, et al.CXCR4 gene transfer enhances the distribution of dermal multipotent stem cells to bone marrow in sublethally irradiated rats[J]. J-Radiat-Res-(Tokyo), 2009 , 50(3): 193-201.
    13. Brenner S , Whiting-Theobald N, Kawai T ,et al .CXCR4 transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells [J]. StemCells,2004, 22 (7) :1128-1133.
    14. Wynn R F, HartC A, Corrad-Perni C, et al . A small proportion of mesenchymal stem cells strongly expresse functionally active CXCR4 receptor capable of promoting migration to bone marrow[J] . Blood , 2004, 104 :2643-2645.
    15. HonczarenkoM, Le Y, SwierkowskiM, et al. Human bone marrow stromal cells exp ress a distinct set of biologically functional chemokine receptors [J]. Stem Cells, 2006, 24 (4): 1030-1041.
    16.张悦,欧来良,程兆康,等.CXCR4基因修饰骨髓间充质干细胞体外迁移实验[J].生物医学工程学杂志, 2009,26(3): 595-600.
    17. Zipori D.Mesenchymal stem cells: harnessing cell plasticity to tissue and organ repair[J]. Blood Cells Mol Dis, 2004, 33 (3) :211-215.
    18. Ohara N, Koyama H , Miyata T, et al . Adenovirus mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia[J] . Gene Ther , 2001 ,8 (11) :837-845.
    19.冯一梅,徐辉.间充质干细胞基因转染的相关研究现状[J].中国组织工程研究与临床康复, 2007, 11(11):2118-2121
    20.孙超,李定国.基因修饰干细胞移植治疗研究现状[J].国外医学内科学分册,2006,33(6):264-267.
    21.刘正山,张成,尚延昌,等.不同基因载体转导人骨髓间充质干细胞比较[J].中国医学科学院学报,2008,30(5): 569– 573.
    1. Rosu-Myles M, Bhatia M. SDF-1 enhances the expansion and maintenance of highly purified human hematopoietic progenitors[J].Hematol J,2003,4(2):137-145.
    2. Horuk R. Chemokines beyond inflamation[J]. Nature,1998 ,393 (6685) :524-525.
    3. Horuk R.Chemokine receptors[J]. Cytokine and Growth Factor Reviews,2001,12(4) 313-335.
    4. Muller A, Homey B,Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis[J]. Nature,2001 ,410 (6824) : 50-56.
    5. Scotton C J ,Wilson J L ,Scott K,et al. Human ovarian cancer : Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer[J].Cancer Res ,2002 ,62 (20) : 5930-5938.
    6. Hideshima T ,Chauhan D ,Hayashi T ,et al. The Biological sequelae of stromal cell-derived factor-1αin multiple myeloma[J]. Mol Cancer Ther ,2002 ,1(7) :539-544.
    7. Taichman R S , Cooper C , Keller E T , et al. Prostate cancer metastasis : Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone[J]. J Biol Chem ,2002 ,277(51) :49481-49487.
    8.杨文博,孔佩艳.趋化因子基质细胞衍生因子(SDF-1)及其受体CXCR4[J].免疫学杂志,2003,19(3):142-144.
    9. Tashiro K,Tada H,Heilker R,et al.A Cloning Strategy for Secreted Proteins and Type I Membrane Proteins [J] .Science,1993,261:600-603.
    10. NagasawaT,Kikutani H,KishimotoT,et al . Molecular Cloning and Structure of a Pre-B-cell Growth-stimulating Factor [J]. Pro Natl Acad Sci USA ,1994,91:2305-2310.
    11. Leichmann M,Gillen C,Czardybon M,et al.Cloning and characterization of SDF-1 chemokine transcipt with developmentally regulated expression in the nervous system [J].Eur J Neuro Sci,2000,12(6):1857-1866.
    12. Hirozu M,Nakano J,Inazawa K. Structure and chromosomal location of the human stromal cell -derived factor 1(SDF-1) gene[J] . Genomics ,1995 ,28 :495.
    13. Loetscher M,Geiser T, O’Reilly T,et al. Cloning of a human seven-transmembrane domain receptor,L ESTR,that is highly expressed in leukocytes [J] . J Biol Chem,1994,269:232.
    14.谭毅,蔡绍皙,马伟峰等. SDF21和及其受体CXCR4的结构与功能[J].中国生物化学与分子生物学报,2004,20 (1) :1-5.
    15. Crump M P,Gong J H,Loetscher P, et al. Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1[J]. EMBO J , 1997 ,16 (23) :6996-7007.
    16. Gupta S K, Pillarisetti K, Thomas R A , et al. Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1α: implications for development of selective CXCR4 antagonists[J].Immunol Lett ,2001 ,78 (1) :29-34.
    17. Loetscher P , Gong J , Dewald B , et al. N-terminal peptides of stromal cell-derived factor-1 with CXC chemokine receptor 4 agonist and antagonist activities[J]. J Biol Chem , 1998 , 273(35) : 22279-22283.
    18. Elisseeva E L , Slupsky C M, Crump M P , et al.NMR studies of active N-terminal peptides of stromal cell-derived factor-1 structural basis for receptor binding[J]. J Biol Chem ,2000 ,275 (35) :26799-26805.
    19. Zhou NM, Luo ZW, Luo J S , et al. Exploring the stereochemistry of CXCR4-peptide recognition and inhibiting HIV-1 entry with D-peptides derivedfrom chemokines[J]. J Biol Chem ,2002 ,277(20) :17476-17485.
    20. Sadir R , Baleux F , Grosdidier A , et al.Characterization of the stromal cell-derived factor-1a-heparin complex[J]. J Biol Chem , 2001 ,276(11) :8288-8296.
    21. Tudan C , Willick G E , Chahal S et al. C-terminal cyclization of an SDF-1 small peptide analogue dramatically increases receptor affinity and activation of the CXCR4 receptor[J]. J Med Chem , 2002 ,45(10) :2024-2031.
    22. Dettin M, Scarinci C , Pasquato A , et al. Synthetic peptides for study of human immunodeficiency virus infection[J]. Appl Biochem Biotechnol ,2002 ,102-103(1-6) : 41-47.
    23. Dragic T. An overview of the determinants of CCR5 and CXCR4 co-receptor function[J]. J Gen Virol , 2001 , 82 (Pt 8) :1807-1814.
    24. Zheng H , Peiper S C , Zhu X H. Structure function correlation of chemokine receptor CXCR4[J]. Acta Acad Med Mili Tertiae ,2001 ,23(2) :185-189.
    25. Roland J ,Murphy B J ,Ahr B,et al .Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling[J]. Blood ,2003 ,101 (2) :399-406.
    26. Huang X Q ,Shen J H ,Cui M,et al. Molecular dynamics simulations on SDF-1a : Binding with CXCR4 receptor[J].. Biophys J ,2003 ,84(1) :171-184.
    27. Zhou N M, Luo Z W, Luo J S ,et al. Structural and functional characterization of human CXCR4 as a chemokine receptor and HIV-1 co-receptor by mutagenesis and molecular modeling studies[J]. J Biol Chem , 2001 ,276 (46) : 42826-42833.
    28. Hatse S , Princen K, Gerlach L O , et al. Mutation of Asp (171) and Asp (262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100 [J]. Mol Pharm , 2001 ,60(1) :164-173.
    29. Gerlach L O , Skerlj R T , Bridger G J , et al. Molecular interactions of cyclam and bicyclam non-peptide antagonists with thebCXCR4 chemokine receptor[J]. J Biol Chem ,2001 , 276 (17) :14153-14160.
    30. Labrosse B ,Treboute C , Brelot A ,et al. Cooperation of the V1/V2 and V3 domains of human immunodeficiency virus type 1 gp120 for interaction with the CXCR4 receptor[J]. J Virol , 2001 ,75 (12) : 5457-5464.
    31. Pontow S , Ratner L. Evidence for common structural determinants of human immunodeficiency virus type 1 coreceptor activity provided through functional analysis of CCR5PCXCR4 chimeric coreceptors[J]. J Virol , 2001 ,75 (23) : 11503-11514.
    32. Zou YR ,Kottmann AH ,Kuruda M, et al . Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development [J] .Nature ,1998 ,393 (6685) : 595-599.
    33. Hesselgesser J ,Taub D ,Baskar P , et al . Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4[J] .Curr Biol ,1998 ,8 (10) :595-598.
    34. Aiuti A ,Webb I ,Bleul C , et al . The chemokine SDF-1 is a chemoattractant for human CD34 hematopoietic progenitor cells and provides a new machenismto exlain the mobilization of CD34 progenitors to peripheral blood[J] . J Exp Med ,1997 , 185(1) :111-120.
    35. Nagasawa T,Hirota S,Tachibana K,et al.Detects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 [J] .Nature,1996 ,382 (6592) :635-638.
    36. Tachibana K,Hirota S ,Iizasa H , et al . The chemokine receptor CXCR4 is essential for vascularzation of the gastrointestinal tract [J] . Nature ,1998 ,393 (6685) :591-594.
    37. Kowalska MA,Rataiczak I,Hoxie J,et al.Megakaryocyte precursors ,megakaryocytes and platelets express the HIV co-receptor CXCR4 on their surface :Determination of response to stromal derived factor-1 by Megakaryocytes and platelets [J]. Br J Haematol,1999,104 (2):220-229.
    38. Yusuf F, Rehimi R, Morosan-Puopolo G,et al. Inhibitors of CXCR4 affect the migration and fate of CXCR4+ progenitors in the developing limb of chick embryos[J].Dev Dyn. 2006 ,235(11):3007-3015.
    39. Ma Q, Jone D,Borghesani PR,et al.Impaired B-lymphopoiesis,myelopoiesis,and derailed cerebellar neuron migration in CXCR4 and SDF-1 deficient mice[J].Proc Natl Acad Sci USA,1998,95(16):9448-9453.
    40. Lataillade JJ,Clay D,Dupuy C,et al.Chemokine SDF-1 enhancescirculating CD34+cell proliferation in synergy with cytokines possible role in rogenitor survival [J]. Blood, 2000, 95 :756-768.
    41. Hendrix CW,Flexner C,MacFarland RT,et al.Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers[J]. Antimicrob Agents Chemother, 2000 , 44(6): 1667-1673.
    42. Vaday GG,Lidey O. Extracellular matrix motictis ,Cytokines ,and enzymes , dynamic effects on immune cell behavior and inflammation[J] . J Leukoe Biol ,2000 , 67 :149-159.
    43. Levesque JP ,Hendy T, Takamatsu Y, et al. Disruption of the CXCR4/ CXCLR chemotactic interaction during hematopoictic stem cell mobilization induced by G-SCF or cyclophosphamide [J] . J C1in Invest ,2003 ,111 :187-196.
    44. Papayannopoulou T , Nakamoto B. Peripheralization ofhemopoietic progenitors in primates treated with antiVLA4 integrin [J] . Proc Natl Acad Sci USA , 1993 , 90(29) :9374.
    45. Sweeney EA , Lortat Jacob H , Priestley GV , et al. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice : involvement in mobilization of stem/progenitor cells[J] . Blood ,2002 ,99 (1) :44.
    46. Frenette PS , Weiss L. Sulfated glycans induce rapid hematopoietic progenitor cellmobilization:evidence for selectin-dependent and independent mechanisms[J]. Blood ,2000 ,96 (7) :2460.
    47. Peled A ,Petit I ,Kollet O , et al. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4[J] . Science ,1999 ,283 (4) :845.
    48. Petit I , Kravitz MS , Nagler A ,et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4[J] . Nature Immunol ,2002 ,3 (5) :687.
    49. Ponomaryov T , Peled A , Petit I , et al. Increased expression of the chemokine SDF-1 following DNA damage : relevance for human stem cell function[J] . J Clin Invest ,2000 ,106 (11) :1331.
    50. Voermans C , Kooi ML , Rodenhui S ,et al. In vitro migratory capacity of CD34 + cells is related to hematopoietic recovery after autologous stem cell transplantation [J] . Blood ,2001 ,97 (3) :799.
    51. Levesque LJ ,Bendall J ,Hendy B ,et al. SDF-1 is inactivated by proteolytic cleavage in the bone marrow of mice mobilized by either G-CSF or cyclophosphamide [J] . Blood , 2001 , 98(4) : 831.
    52. Delgado M ,Lewis IC ,Loetscher P , et al. Rapid inactivation of stromal cell2derived factor21 by cathepsin G associated with lymphocytes[J] . Eur J Immunol ,2001 ,31 (6) :699.
    53. Lapidot T, Dar A, Kollet O.How do stem cells find their way home? [J]. Blood. 2005, 106(6):1901-1910.
    54. Peled A ,Grabovsky V ,Habler L ,et al. The chemokine SDF-1 stimulates integrin- mediated arrest of CD34 ( + ) cells on vascular endothelium under shear flow[J]. J Clin Invest ,1999 ,104 (9) :1199.
    55. Kim CH ,Broxmeyer HE. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants : stromal cell-derived factor-1 , steel factor , and the bone marrow environment[J] .Blood ,1998 ,91 (1) :100
    56. Hoichi H ,Beate H , Kei T ,et al. Plasma elevation of SDF-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells[J]. Blood ,2001 ,97 (11) :3354
    57. Carion A , Iochman S ,Charbord P ,et al. Differential expression patterns of SDF-1 andMMP-9 by human bone marrow stromal and endothelial cells before and after stimulation by G- or M-CSF[J] . ExpHematol ,2002 ,30 (6):190
    58. Naiyer JA ,Jo DY,Ahn J , et al. Stromal derived fator-1-induced chemokinesis of cord blood CD34 ( + ) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin[J].Blood ,1999 ,94 (12) :4011
    59. Voermans C ,Rood PML ,Hordijk PL ,et al. Adhesion molecules involved in transendothelial migration of human hematopoietic progenitor cells[J]. Stem Cells , 2000 ,18 (6) :435
    60. Peled A ,Kollet O ,Ponomaryov T ,et al. The chemokine SDF21 activates the intrgrins L FA-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
    61. Jin FY, Qiu LG, Li QC, et al.The effect of matrix metalloproteinase-9 in granulocyte colony stimulation factor-induced stem cell mobilization[J].Zhonghua Yi Xue Za Zhi. 2006 Nov 14;86(42):2966-2970.
    62. Voermans C ,Anthony EC ,Mul E ,et al. SDF-1-induced actin poly-merization and migration in hematopoietic progenitor cells[J]. Exp Hematol ,2001 ,29 (12) :1456
    63. Gotoh A ,Reid S ,Miyazawa K,et al. SDF-1 suppresses cytokine-induced adhesion of human haemopoietic progenitor cells to immobilized fibronectin[J].Br J Haematol , 1999 ,106 (1) :171
    64. 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
    65. Kollet O , Spiegel A , Peled A ,et al. Rapid and efficient homing of human CD34 ( + ) CD 38 ( - / low) CXCR4 ( + ) stem and progenitor cells to the bone marrow and spleen of NOD/ SCID and NOD/ SCID/ B2mnull mice[J].Blood ,2001 ,97 (10) :3283
    66. Jinquan T,Quan S, Jacobi H H ,et al.CXC chemokine receptor 4 expression and stromal cell-derived factor-1alpha-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 and interleukin-10[J]. Immunology, 2000 Mar; 99(3): 402-410.
    67. Yonezawa A,Hori T,Sakaida H, et al.SDF-1 has costimulatory effects on human T cells: possible involvement of MAPK (ERK2) activation[J]. Microbiol-Immunol, 2000,44(2):135-141.
    68. Nanki T, Hayashida K, El-Gabalawy HS,et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium[J].J Immunol, 2000 ,165(11):6590-6598.
    69. Dunussi-Joannopoulos K, Zuberek K, Runyon K, et al.Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses[J].Blood, 2002 , 100(5): 1551-8.
    70. Gonzalo J A,Lloyd C M,Peled A,et al.Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease[J]. J Immunol, 2000, 165(1): 499-508.
    71. Clissi B,D'Ambrosio D, Geginat J,et al.Chemokines fail to up-regulate beta 1 integrin-dependent adhesion in human Th2 T lymphocytes[J]. J Immunol, 2000 , 164(6): 3292-3300.
    72. Burns JM, Summers BC, Wang Y, et al.A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med, 2006,203(9):2201-2213.
    73. Kang H, Watkins G, Parr C,et al. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer[J]. Breast Cancer Res, 2005,7(4): R402-410.
    74. Orimo A, Gupta PB, Sgroi DC,et al.Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion[J]. Cell, 2005,121(3):335-348.
    75. Phillips RJ,Burdick MD,Lutz M,et al.The stromal cell derived factor -1/CXCL-CXC chemokine receptor 4 biological axis nosmall cell lung cancer metastases[J]. Am J Respir Crit Care Med,2003,167(12):1676-1686.
    76. Libura J,Drukala J,Majka M,et al.CXCR4/SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion,chemotaxis,and adhesion[J]. Blood, 2002,100(7) :2597-2606.
    77. Sanz Rodriguez F,Hidalgo A,Teixido J. Chemokine stromal cell-derived factor-1 alphamodulates VLA-4 integin-mediated multiple myeloma cell adhsion to CS-1/fibronection and VACM[J]. Blood, 2001, 97(2):346-351.
    78.储子彦,陈晓萍,方晶晶.趋化因子SDF-1及受体CXCR4研究进展[J].生物学杂志,2006, 23 (1):11-13.
    79. Kucia M, Reca R, Miekus K,et al.Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis[J].Stem Cells, 2005,23(7):879-894.
    80. Ratajczak MZ, Reca R, Wysoczynski M, et al. Modulation of the SDF-1-CXCR4 axis by the third complement component (C3)--implications for trafficking of CXCR4+ stem cells[J]. Exp Hematol, 2006,34(8):986-995.
    81. Liu DD, Shyu WC, Lin SZ.Stem cell therapy in stroke: strategies in basic study and clinical application[J]. Acta Neurochir Suppl, 2006;99:137-139.
    82. Shyu WC, Lee YJ, Liu DD,et al. Homing genes, cell therapy and stroke[J]. Front Biosci, 2006 ,11:899-907.
    83. Dalakas E, Newsome PN, Harrison DJ,et al. Hematopoietic stem cell trafficking in liver injury[J]. FASEB J,2005 ,19(10):1225-1231.
    84. Ponte A L, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities[J]. Stem Cells, 2007,25(7):1737-1745.
    85. Misao Y, Arai M, Ohno T, et al.Modification of post-myocardial infarction granulocyte -colony stimulating factor therapy with myelo-suppressives[J]. Circ J, 2007,71(4):580-590.
    86. Abbott JD, Huang Y, Liu D,et al. Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury[J]. Circulation, 2004,110(21):3300-3305.
    87. Deng ZR, Yang C, Ma AQ,et al.Dynamic changes of plasma VEGF, SDF-1 and peripheral CD34+ cells in patients with acute myocardial infarction[J]. Nan Fang Yi Ke Da Xue Xue Bao,2006,26(11):1637-1640.
    88. Jung YJ, Ryu KH, Cho SJ,et al. Syngenic bone marrow cells restore hepatic function in carbon tetrachloride-induced mouse liver injury[J]. Stem Cells ,2006 ,15(5):687-695.
    89. Shiba Y, Takahashi M, Yoshioka T, et al.M-CSF accelerates neointimal formation in theearly phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system[J]. Arterioscler Thromb Vasc Biol,2007,27(2):263-265.
    90. Zong ZW, Cheng TM, Su YP,et al.Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal multipotent cells to sublethally irradiated bone marrow[J]. J Radiat Res (Tokyo),2006,47(3-4):287-293.
    91. Brzoska E, Grabowska I, Hoser G, et al.Participation of stem cells from human cord blood in skeletal muscle regeneration of SCID mice[J]. Exp Hematol, 2006 ,34(9): 1262-1270.
    92. Wang Y, Haider HKh, Ahmad N, et al. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts[J]. J Mol Cell Cardiol, 2006 ,41(3): 478-487.
    93. Lee SP, Youn SW, Cho HJ, et al. Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue[J]. Circulation, 2006 ,114(2):150-159.
    94. Kucia M, Wojakowski W, Reca R, et al.The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner[J]. Arch Immunol Ther Exp (Warsz), 2006,54(2):121-135.
    95. Li Y, Reca RG, Atmaca-Sonmez P, et al. Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells[J]. Invest Ophthalmol Vis Sci, 2006 ,47(4):1646-1652.
    96. Togel F, Isaac J, Hu Z, et al.Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury[J].Kidney Int,2005,67(5): 1772-1784.
    97. Ji JF, He BP, Dheen ST, et al.Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury[J]. Stem Cells, 2004,22(3):415-427.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700