自体骨髓单个核细胞治疗脊髓损伤的临床研究
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摘要
目的研究证明,骨髓来源的单个核细胞(bone marrow-derivedmononuclear cells,MNCs)所包含的多种骨髓干细胞可作为多潜能干细胞对脊髓外伤或缺血性损伤等造成的功能缺失具有显著的治疗作用。康复训练对于脊髓损伤患者肌力、日常生活活动能力以及膀胱功能等神经功能的改善具有一定作用,但对脊髓损伤的修复作用有限。本文采用自体骨髓单个核细胞移植方法结合康复训练治疗脊髓损伤患者,观察其近期疗效和安全性。
方法34例脊髓损伤患者,采用随机表法分为移植组和对照组。移植组16例,对照组18例,均经CT或MRI确诊并行手术或非手术治疗。感觉、运动功能评定采用美国脊柱损伤协会(American Spinal InjuryAssociation,ASIA)分级,脊髓损伤程度采用脊髓损伤神经学分类国际标准(International Standards for Neurological Classification of SpinalCord Injury)(第六版,2006)进行评定。两组在年龄、病程、损伤程度等方面均具有可比性(P＞0.05)。患者知情同意并签署知情同意书。移植组在综合康复治疗的基础上给予自体MNCs治疗,经髂骨穿刺采集自体骨髓,分离提取MNCs后经静脉或蛛网膜下腔注射,同时静脉滴注复方丹参20mL。对照组在综合康复治疗的基础上给予生理盐水250mL,静脉滴注。两组均于入院当天、治疗后7,15,30,60,90d进行运动与感觉功能、日常生活活动能力、膀胱功能评定。
结果①移植组感觉、运动功能、日常生活活动能力和膀胱功能均有改善,但与对照组比较,统计学差异无显著性意义。②ASIA分级评定:移植组ASIA分级A级9例,有2例在第90天评估中恢复为B级。B级3例,1例在第90天评估中恢复为C级。C级2例,1例在第30天评估中恢复为D级,第90天评估中恢复为E级,能独立行走,生活完全自理。D级2例,其中1例在第90天评估中恢复为E级。对照组A级8例,1例在第90天评估中恢复为B级。B级5例,治疗后无变化。C级3例,1例在第90天评估中恢复为D级。D级2例,在第90天评估中恢复为E级。两组其余患者治疗后ASIA分级无变化。两组比较,经Ridit分析,u=0.07,P=0.94,差异无显著性意义。③日常生活活动能力评分:采用改良Bathel指数(Modified Bathel Index,MBI)。经过干细胞移植治疗和系统康复训练,与治疗前相比,移植组(F=57.31)和对照组(F=52.08)患者的MBI评分均有显著提高,经统计学处理,均P＜0.001,差异有显著性意义。但两组之间比较无差异(P＞0.05)。④膀胱功能:移植组12例恢复自主排尿,时间平均为(56.7±8.6)d,对照组9例,平均为(61.3±7.9)d,两组比较经统计学处理,P＞0.05,差异无显著性意义;移植组患者有8例出现尿失禁,6例在治疗后15d、2例在第30天评估时症状消失,对照组8例,在第90天评估时3例症状消失,5例无变化。采用间歇清洁导尿方法训练膀胱功能,两组患者残余尿量均有显著减少,治疗前、后比较,均P＜0.001,差异有非常显著性意义。但两组之间比较无差异;⑤MNCs移植的不良反应,包括蛛网膜下腔移植后出现低热9例,头痛4例,腹胀1例:1例患者在注射后出现双下肢麻木、脑膜刺激征。经对症处理均于72小时内消失。
结论自体骨髓MNCs移植治疗脊髓损伤近期有一定疗效,安全可行。
Objective To observe the short-term curative effect and safety of autologous bone marrow-derived mononuclear cells (MNCs) transplantation on patients with spinal cord injury (SCI).
Methods Total 34 inpatients with SCI were randomly divided into transplantation group and control group. The patients knew the experiment and signed the consent. A total of 16 cases in the transplantation group and 18 cases in the control group were diagnosed with CT or MRI. It was comparable between the two group in age, course of disease, degree of injury (ASIA rating) (P>0.05). On the basis of comprehensive rehabilitation treatment, those in the transplantation group received autologous MNCs transplantation. The bone marrow (160-280mL) was harvested from the patients' ilia and then MNCs were isolated. The MNCs were injected intravenously or into subarachnoid space by lumbar puncture. Those in the control group received comprehensive rehabilitation treatment and NS 250mL intravenously. Motor and sense function, activity of daily living (ADL) and bladder function were evaluated on the first day of rehabilitation, 7,15,30,60 and 90 days after treatment in the two groups. Neurological function of the patients with spinal cord injury were evaluated by American Spinal Injury Association (ASIA) and International Standards for Neurological Classification of Spinal Cord Injury (Edit 6~(th), 2006).
Results Totally 34 patients were involved in the result analysis.①After transplantation of MNCs and rehabilitation treatment, the scales of sense, motor and autonomic nerve function were improved to some extent in 16 patients of transplantation group and 18 of control group. There were no significant differences statistically between the two groups in scales of the sense, motor, MBI and bladder function.②In the transplantation group, there were 5 cases elevated 1-2 grades respectively on the 90th day, In the control group, there were 4 cases elevated 1 grade respectively on the 90th day. But there were no significant differences statistically by Ridit analyses(u=0.07, P=0.94).③The side-effects of the MNCs transplantation included fever (9 cases), headache (4 cases), and abdominal dissension (1 cases). Of them, 1 case appeared numbness in his legs and meningeal stimulation after subarachnoid space injection, and disappeared within two or three days.
Conclusion MNCs transplantation in the treatment of SCI is effective and safe in short term, but long-term curative effect needs more observation.
方法34例脊髓损伤患者,采用随机表法分为移植组和对照组。移植组16例,对照组18例,均经CT或MRI确诊并行手术或非手术治疗。感觉、运动功能评定采用美国脊柱损伤协会(American Spinal InjuryAssociation,ASIA)分级,脊髓损伤程度采用脊髓损伤神经学分类国际标准(International Standards for Neurological Classification of SpinalCord Injury)(第六版,2006)进行评定。两组在年龄、病程、损伤程度等方面均具有可比性(P＞0.05)。患者知情同意并签署知情同意书。移植组在综合康复治疗的基础上给予自体MNCs治疗,经髂骨穿刺采集自体骨髓,分离提取MNCs后经静脉或蛛网膜下腔注射,同时静脉滴注复方丹参20mL。对照组在综合康复治疗的基础上给予生理盐水250mL,静脉滴注。两组均于入院当天、治疗后7,15,30,60,90d进行运动与感觉功能、日常生活活动能力、膀胱功能评定。
结果①移植组感觉、运动功能、日常生活活动能力和膀胱功能均有改善,但与对照组比较,统计学差异无显著性意义。②ASIA分级评定:移植组ASIA分级A级9例,有2例在第90天评估中恢复为B级。B级3例,1例在第90天评估中恢复为C级。C级2例,1例在第30天评估中恢复为D级,第90天评估中恢复为E级,能独立行走,生活完全自理。D级2例,其中1例在第90天评估中恢复为E级。对照组A级8例,1例在第90天评估中恢复为B级。B级5例,治疗后无变化。C级3例,1例在第90天评估中恢复为D级。D级2例,在第90天评估中恢复为E级。两组其余患者治疗后ASIA分级无变化。两组比较,经Ridit分析,u=0.07,P=0.94,差异无显著性意义。③日常生活活动能力评分:采用改良Bathel指数(Modified Bathel Index,MBI)。经过干细胞移植治疗和系统康复训练,与治疗前相比,移植组(F=57.31)和对照组(F=52.08)患者的MBI评分均有显著提高,经统计学处理,均P＜0.001,差异有显著性意义。但两组之间比较无差异(P＞0.05)。④膀胱功能:移植组12例恢复自主排尿,时间平均为(56.7±8.6)d,对照组9例,平均为(61.3±7.9)d,两组比较经统计学处理,P＞0.05,差异无显著性意义;移植组患者有8例出现尿失禁,6例在治疗后15d、2例在第30天评估时症状消失,对照组8例,在第90天评估时3例症状消失,5例无变化。采用间歇清洁导尿方法训练膀胱功能,两组患者残余尿量均有显著减少,治疗前、后比较,均P＜0.001,差异有非常显著性意义。但两组之间比较无差异;⑤MNCs移植的不良反应,包括蛛网膜下腔移植后出现低热9例,头痛4例,腹胀1例:1例患者在注射后出现双下肢麻木、脑膜刺激征。经对症处理均于72小时内消失。
结论自体骨髓MNCs移植治疗脊髓损伤近期有一定疗效,安全可行。
Objective To observe the short-term curative effect and safety of autologous bone marrow-derived mononuclear cells (MNCs) transplantation on patients with spinal cord injury (SCI).
Methods Total 34 inpatients with SCI were randomly divided into transplantation group and control group. The patients knew the experiment and signed the consent. A total of 16 cases in the transplantation group and 18 cases in the control group were diagnosed with CT or MRI. It was comparable between the two group in age, course of disease, degree of injury (ASIA rating) (P>0.05). On the basis of comprehensive rehabilitation treatment, those in the transplantation group received autologous MNCs transplantation. The bone marrow (160-280mL) was harvested from the patients' ilia and then MNCs were isolated. The MNCs were injected intravenously or into subarachnoid space by lumbar puncture. Those in the control group received comprehensive rehabilitation treatment and NS 250mL intravenously. Motor and sense function, activity of daily living (ADL) and bladder function were evaluated on the first day of rehabilitation, 7,15,30,60 and 90 days after treatment in the two groups. Neurological function of the patients with spinal cord injury were evaluated by American Spinal Injury Association (ASIA) and International Standards for Neurological Classification of Spinal Cord Injury (Edit 6~(th), 2006).
Results Totally 34 patients were involved in the result analysis.①After transplantation of MNCs and rehabilitation treatment, the scales of sense, motor and autonomic nerve function were improved to some extent in 16 patients of transplantation group and 18 of control group. There were no significant differences statistically between the two groups in scales of the sense, motor, MBI and bladder function.②In the transplantation group, there were 5 cases elevated 1-2 grades respectively on the 90th day, In the control group, there were 4 cases elevated 1 grade respectively on the 90th day. But there were no significant differences statistically by Ridit analyses(u=0.07, P=0.94).③The side-effects of the MNCs transplantation included fever (9 cases), headache (4 cases), and abdominal dissension (1 cases). Of them, 1 case appeared numbness in his legs and meningeal stimulation after subarachnoid space injection, and disappeared within two or three days.
Conclusion MNCs transplantation in the treatment of SCI is effective and safe in short term, but long-term curative effect needs more observation.
引文
[1]Garbossa D,Fontanella M,Fronda C,et al.New Strategies for repairing the injured spinal cord:the role of stem cells.Neurol Res 2006;28(5):500-504.
[2]Barry FP.Biology and clinical applications of mesenchymal stem cells.Birth Defects Res C Embryo Today 2003;69(3):250-256.
[3]Horner PJ,Gage FH.Regenerating the damaged central nervous system.Nature 2000;407:963-970.PMID:11069169
[4]Weiss S,Dunne C,Hewson J,et al.Multipotent CNS stem cells are present in the adult mammalian spinal cord.J NeuroSci 1996;16:7599-7609.PMID:8922416
[5]Shihabuddin LS,Ray J,Gage FH.FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord.Exp Neurol 1997;148:577-586.PMID:9417834
[6]Horky LL,Galimi F,Gage FH,et al.Fate of endogenous stem/progenitor cells following spinal cord injury.J Comp Neurol.2006 Oct 1;498(4):525-38.PMID:16874803
[7]Alonso G.NG2 proteoglycan-expressing cells of the adult rat brain:possible involvement in the formation of glial scar astrocytes following stab wound.Gila 2005;49:318-338.PMID:15494983
[8]Chernykh ER,Stupak VV,Muradov GM,et al.Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients.Bull Exp Biol Med.2007 Apr;143(4):543-7.PMID:18214319
[9]Callera F,do Nascimento RX.Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury:a preliminary safety study.Exp Hematol.2006 Feb;34(2):130-131.PMID:16459180
[10]Deda H,Inci MC,K(u|¨)rekci AE,et al.Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up.Cytotherapy.2008;10(6):565-74.PMID:18615345
[11]崔贵祥,李义召,高华,等.自体骨髓间充质干细胞治疗神经系统疾病初步研究.中国康复理论与实践,2006,12(3):242-245.
[12]谢遵伟,崔贵祥,李义召,等.自体骨髓间充质干细胞治疗脊髓损伤疗效观察.中国组织工程研究与临床康复,2007,11(7):1277-1279.
[13]Sykova E,Homola A,Mazanec R,et al.Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.Cell Transplant 2006;15(8-9):675-687.PMID:17269439
[14]Saito F,Nakatani T,Iwase M,et al.Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation:the first clinical trial case report.J Trauma.2008 Jan;64(1):53-59.PMID:18188099
[15]Callera F,de Melo CM.Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury:CD34+ cells' migration into the injured site.Stem Cells Dev 2007;16(3):461-466.PMID:17610376
[16]Moviglia GA,Varela G,Brizuela JA,et al.Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.Spinal Cord. 2009 Feb 17. [Epub ahead of print] PMID: 19223861
[17]Yoon SH, Shim YS, Park YH, Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial.Stem Cells. 2007 Aug;25(8):2066-73. Epub 2007 Apr 26. PMID: 17464087
[18]Hamano K, Nishida M, Hirata K,et al.Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001 Sep;65(9):845-7.
[19]Strauer BE, Brehm M, Zeus T,et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr. 2001 Aug 24;126(34-35):932-8.
[20]Strauer BE, Brehm M, Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002 Oct 8;106(15):1913-8.
[21]Wollert KC, Meyer GP, Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.Lancet. 2004 Jul 10-16;364(9429):141-8.
[22]Carvalho KA, Cunha RC, Vialle EN, et al. Functional outcome of bone marrow stem cells (CD45~+/CD34) after cell therapy in acute spinal cord injury: in exercise training and sedentary rats. Transplant Proc. 2008 Apr;40(3):847-849.
[23]Carvalho KA, Vialle EN, Moreira GH.et al. Functional outcome of bone marrow stem cells (CD45~+/CD34~-) after cell therapy in chronic spinal cord injury in Wistar rats.Transplant Proc. 2008 Apr;40(3):845-846.
[24]Modo M, Stroemer RP, Tang E, et al. Effects of implantation site of stem cell grafts on behaveoval recovery from stroke damage. Stroke 2002;33(9):2270-2278.
[25]Vaquero J, Zurita M, Oya S,et al. Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration? Neurosci Lett. 2006 May 1;398(1-2): 129-34.
[26]Dezawa M, Kanno H, Hoshino M, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest. 2004;113(12):1701-10.
[27]Sheth RN, Manzano G, Li X,et al. Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats. J Neurosurg Spine. 2008 Feb;8(2):153-62.
[28]Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine.2004 Sep 15;29(18):1971-1979.
[29]Ankeny DP, McTigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004 Nov;190(1):17-31.
[30]Yano S, Kuroda S, Lee JB, et al. In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.J Neurotrauma. 2005 Aug;22(8):907-18.PMID: 16083357
[31]Koda M, Okada S, Nakayama T, et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice.Neuroreport. 2005 Nov 7;16(16):1763-7.
[32]Yoshihara T, Ohta M, Itokazu Y.et al. Neuroprotective effect of bone marrow-derived mononuclear cells promoting functional recovery from spinal cord injury. J Neurotrauma. 2007 Jun;24(6): 1026-36.
[33]lsele NB, Lee HS, Landshamer S, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.Neurochem Int. 2007 Jan;50(1):243-50. Epub 2006 Oct 16. PMID: 17050038
[34] Dasari VR, Spomar DG, Cady C, et al. Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats. Neurochem Res 2007;32(12): 2080-2093. PMID: 17564836
[35]Yamasaki K, Setoguchi T, Takenouchi T, et al. Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury.Spine. 2009 Feb 15;34(4):323-7. PMID: 19182706
[36]Mahmood A, Lu D, Chopp M. Intravenous administration of marrow stromal cells (MSCs) increase the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 2004;21(1):33-39.
[37]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cells support extensive axonal growth at sotes of spinal cord injury.Exp Neurol. 2005;191(2):344-360.
[38]Neuhuber B, Timothy Himes B, Shumsky JS, et al. Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res. 2005 Feb 21;1035(1):73-85.
[39]Xiang S, Pan W, Kastin AJ. Strategies to creat a regenerating enviroment for the injured spinal cord. Curr Pharm Des,2005,11(10):1267-1277.
[40]Lu P, Jones LL, Tuszynski MH. Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol. 2007 Jan;203(1):8-21.
[41]Tao H,Rao R,Ma DD.Cytokine-induced stable neuronal differentiation of human bone marrow mesenchymal stem cells in a serum/feeder cell-free condition.Dev Growth Differ 2005;47(6):423-433.
[42]Zhang J,Li Y,Chopp M.Exprssion of insulin-like growth factor 1and receptor in ischemic rats treated with human marrow stromal cells.Brain Res 2004;1030(1):19-27.
[43]李长德,杨建华,刘铮,李东平.骨髓单个核细胞移植治疗急性脊髓损伤[J].中国组织工程研究与临床康复,2008,8(8):1431-1434.
[44]Shi E,Kazui T,Jiang X,et aI.Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord.Ann Thorac Surg.2007 Apr;83(4):1484-1490.
[45]Fan L,DU F,Cheng BC,et al.Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques.Chin J Traumatol.2008 Apr;11(2):94-7.PMID:18377712
[1]Alonso G.NG2 proteoglycan-expressing cells of the adult rat brain:possible involvement in the formation of glial scar astrocytes following stab wound.Glia 2005;49:318-338.PMID:15494983
[2]Garbossa D,Fontanella M,Fronda C,et al.New Strategies for repairing the injured spinal cord:the role of stem cells.Neurol Res 2006;28(5):500-504.
[3]Barry FP.Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 2003;69(3):250-256.
[4]Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature 2000; 407: 963-970. PMID: 11069169
[5]Weiss S, Dunne C, Hewson J, et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord. J NeuroSci 1996;16:7599-7609. PMID: 8922416
[6]Shihabuddin LS, Ray J, Gage FH. FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp Neurol 1997;148:577-586. PMID: 9417834
[7]Horky LL, Galimi F, Gage FH, et al. Fate of endogenous stem/progenitor cells following spinal cord injury.J Comp Neurol.2006 Oct 1;498 (4): 525-38. PMID: 16874803
[8]Sigurjonsson OE, Perreault MC, Egeland T, et al. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord.Proc NatI Acad Sci U S A.2005 Apr 5; 102 (14): 5227-32. Epub 2005 Mar 24. PMID: 15790679
[9]Wright KT, Masri WE, Osman A, et al. The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury:implications for future cell transplantation therapy.Spinal Cord. 2008 Dec;46(12):811-7. Epub 2008 Jun 17. PMID: 18560372
[10]Kamishina H, Cheeseman JA, Clemmons RM. Nestin-positive spheres derived from canine bone marrow stromal cells generate cells with early neuronal and glial phenotypic characteristics.In Vitro Cell Dev Biol Anim. 2008 May-Jun;44(5-6): 140-4. Epub 2008 Apr 9. PMID: 18398665
[11]Neuhuber B, Swanger SA, Howard L, et al. Effects of plating density and culture time on bone marrow stromal cell characteristics.Exp Hematol. 2008 May 19. [Epub ahead of print] PMID: 18495329
[12]李栋,沈柏均,侯怀水,等.兔骨髓间充质干细胞的生物学牲及其 对不同生长因子的反应.中国实验血液学杂志[J].2006,14(5):964-968.
[13]王忠 高毅 汪艳,等.人骨髓间充质干细胞的分离培养与鉴定.中华神经医学杂志[J].2006,5(10):973-977.
[14]王红梅,郭光华.骨髓间充质干细胞的生物学特性.江西医学院学报[J].2006,46(5):169-172.
[15]David CC,Reiner C,Carla M et al.Rapid expansion of fecycling stem cells in cultrues of plastic adherent cells from human bone marrow[J].Proc Natl Acad Sci USA,2000,97(7):3213-3218.
[16]Pittenger F,Mackay A,Beck S et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284143-284147.
[17]Bruder SP,Jaiswal N,Haynesworth SE.Growth kinetics,self renewal,and the osteogenic potrential of purified human mesenchymal stem cells during extensive subculativation and following cryopreservation[J].J Cell Biochem,1997,64:278-294.
[18]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.
[19]Anselme K,Noel B,Flautre B et aI.Association of porous hydroxyapapite and bone marrow cells for bone regeneration[J].Bone,1999,25(2):51-54.
[20]Conget PA,Minguell JJ.Phenotypical and functional properties of huamn bone marrow mesenchymal progenitor cells[J].J Cell Physiol,1999,181(1):67-73.
[21]程朝辉,郑启新,郭晓东,等.不同诱导剂对骨髓间充质干细胞向神经元分化的影响[J].中国骨与关节损伤杂志,2007,22(2):119-121.
[22]Zhang W,Zeng YS,Zhang XB,et al.Combination of adenoviral vector-mediated neurotrophin-3 gene transfer and retinoic acid promotes adult bone marrow cells to differentiate into neuronal phenotypes.NeuroSci Lett.2006 Nov 13;408(2):98-103.Epub 2006 Sep 25.PMID:16996685
[23]Rooney GE,Moran C,McMahon SS,et al.Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid(PLGA) substrate.Tissue Eng PartA.2008 May;14(5):681-90.PMID:18402551
[24]Bi XB,Deng YB,Gan DH,et al.Salvianolic acid B promotes survival of transplanted mesenchymal stem cells in spinal cord-injured rats.Acta Pharmacol Sin.2008 Feb;29(2):169-76.PMID:18215345
[25]董立华,王勇,陆长青,等.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞的研究[J].四川大学学报:医学版,2007,38(3):417-420.
[26]王明宁,林洪,胡琳,等.香丹注射液对大鼠骨髓间充质干细胞的增殖作用[J].华西药学杂志,2007,22(3):304-305.
[27]赵汉宁.鹿茸精诱导大鼠骨髓间充质干细胞分化为神经元样细胞[J].现代医药卫生,2007,23(1):3-5.
[28]Carvalho KA,Vialle EN,Moreira GH,et aI.Functional outcome of bone marrow stem cells(CD45(+)/CD34(-)) after cell therapy in chronic spinal cord injury in Wistar rats.Transplant Proc.2008Apr;40(3):845-6.PMID:18455033
[29]Urdzikova L,Jendelova P,Glogarova K,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.PMID:16958589
[30]Chernykh ER,Stupak W,Muradov GM,et al.Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients.Bull Exp Biol Med.2007 Apr;143(4):543-7.PMID:18214319
[31]Callera F,do Nascimento RX.Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury:a preliminary safety study.Exp Hematol.2006 Feb;34(2):130-131.PMID:16459180
[32]Koshizuka S,Okada S,Okawa A,et al.Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice.J Neuropathol Exp Neurol.2004 Jan;63(1):64-72.PMID:14748562
[33]Koda M,Okada S,Nakayama T,et al.Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice.Neuroreport.2005Nov 7;16(16):1763-7.PMID:16237323
[34]Deda H,Inci MC,K(u|¨)rekci AE,et al.Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up.Cytotherapy.2008;10(6):565-74.PMID:18615345
[35]Satake K,Lou J,Lenke LG.Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue.Spine.2004 Sep 15;29(18):1971-9.PMID:15371697
[36]Sheth RN,Manzano G,Li X,et al.Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats.J Neurosurg Spine.2008 Feb;8(2):153-62.PMID:18248287
[37]吴佳奇,冯大雄,杨天府,等.骨髓间充质干细胞经蛛网膜下腔移植治疗大鼠脊髓损伤及其对T细胞亚群影响的研究[J].中国修复重建外科杂志,2007,21(5):492-496
[38]Deng YB,Liu XG,Liu ZG,et al.Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery:evidence from a study in rhesus monkeys.Cytotherapy.2006;8(3):210-4.PMID:16793730
[39]崔贵祥,李义召,高华,等.自体骨髓间充质干细胞治疗神经系统疾病初步研究.中国康复理论与实践,2006,12(3):242-245.
[40]谢遵伟,崔贵祥,李义召,等.自体骨髓间充质干细胞治疗脊髓损伤疗效观察.中国组织工程研究与临床康复,2007,11(7):1277-1279.
[41]Bakshi A,Barshinger AL,Swanger SA,et al.Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion:a novel method for minimally invasive cell transplantation.J Neurotraumao 2006 Jan;23(1):55-65.PMID:16430372
[42]Sykova E,Homola A,Mazanec R,et al.Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.Cell Transplant 2006;15(8-9):675-687.PMID:17269439
[43]Saito F,Nakatani T,Iwase M,et al.Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation:the first clinical trial case report.J Trauma.2008 Jan;64(1):53-59.PMID:18188099
[44]Koda M,Kamada T,Hashimoto M,et al.Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord.Eur Spine J.2007 Dec;16(12):2206-2214.Epub 2007Sep 21.PMID:17885772
[45]Ronsyn MW,Daans J,Spaepen G,et al.Plasmid-based genetic modification of human bone marrow-derived stromal cells:analysis of cell survival and transgene expression after transplantation in rat spinal cord.BMC Biotechnol.2007 Dec 14;7:90.
[46]Fan L,DU F,Cheng BC,et al.Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques.Chin J Traumatol.2008 Apr;11(2):94-7.PMID:18377712
[47]Yano S,Kuroda S,Lee JB,et al.In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.J Neurotrauma.2005 Aug;22(8):907-18.PMID:16083357
[48]白金柱,刘忠军,丁为民,等.多巴胺D_2受体正电子发射计算机短程显像示踪兔脊髓内移植的神经前体细胞[J].中华医学杂志,2006,86(29):2060-2064
[49]Sykova E,Jendelova P.In vivo tracking of stem cells in brain and spinal cord injury.Prog Brain Res.2007;161:367-83.PMID:17618991
[50]Callera F,de Melo CM.Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury:CD34+ cells' migration into the injured site.Stem Cells Dev 2007;16(3):461-466.PMID:17610376
[51]Yoshihara T,Ohta M,Itokazu Y,et al.Neuroprotective effect of bone marrow-derived mononuclear cells promoting functional recovery from spinal cord injury.J Neurotrauma.2007 Jun;24(6):1026-36.PMID:17600518
[52]Yano S,Kuroda S,Shichinohe H,et al.Bone marrow stromal cell transplantation preserves gammaamino- butyric acid receptor function in the injured spinal cord.J Neurotrauma.2006Nov;23(11):1682-92.PMID:17115913
[53]Rouleau P, Ung RV, Lapointe NP, et al. Hormonal and immunological changes in mice after spinal cord injury.J Neurotrauma. 2007 Feb;24(2):367-78. PMID: 17376000
[54]lversen PO, Hjeltnes N, Holm B, et al. Depressed immunity and impaired proliferation of hematopoietic progenitor cells in patients with complete spinal cord injury.Blood. 2000 Sep 15;96(6):2081-3.PMID: 10979951
[55]Fleming JC, Norenberg MD, Ramsay DA.et al. The cellular inflammatory response in human spinal cords after injury.Brain.2006 Dec;129(Pt 12):3249-69. Epub 2006 Oct 28. PMID:17071951
[56]Moviglia GA, Varela G, Gaeta CA.Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells.Cytotherapy. 2006;8(3):196-201. PMID: 16793728
[57]Yamasaki K, Setoguchi T, Takenouchi T, et al. Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury.Spine. 2009 Feb 15;34(4):323-7. PMID: 19182706
[58]lsele NB, Lee HS, Landshamer S, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.Neurochem Int. 2007 Jan;50(1):243-50. Epub 2006 Oct 16. PMID: 17050038
[59]Dasari VR, Spomar DG, Cady C, et al. Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats. Neurochem Res 2007;32(12): 2080-2093. PMID: 17564836
[60]Sasaki M, Honmou O, Akiyama Y, et al. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons.Glia. 2001 Jul;35(1):26-34. PMID: 11424189
[61]Akiyama Y, Radtke C, Honmou O, Remyelination of the spinal cord following intravenous delivery of bone marrow cells.Glia. 2002 Sep;39(3):229-36. PMID: 12203389
[62]Cao Q, Ding P, Lu J, et al. 2\ 3'-Cyclic nucleotide 3'-phosphodiesterase cells derived from transplanted marrow stromal cells and host tissue contribute to perineurial compartment formation in injured rat spinal cord.J NeuroSci Res. 2007 Jan;85(1):116-30. PMID: 17061258
[63]Blesch A, Tuszynski MH. Transient growth factor delivery sustains regenerated axons after spinal cord injury. J NeuroSci 2007,27(39):10535-10545.
[64]Lu P, Jones LL, Tuszynski MH. Axon regeneration through scars and into sites of chronic spinal cord injury.Exp Neurol. 2007 Jan;203(1):8-21. Epub 2006 Oct2. PMID: 17014846
[65]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury.Exp Neurol.2005 Feb;191(2):344-60. PMID: 15649491
[66]Kim KN, Oh SH, Lee KH, et al. Effect of human mesenchymal stem cell transplantation combined with growth factor infusion in the repair of injured spinal cord. Acta Neurochir Suppl 2006;99:133-136.
[67]Ao Q, Wang AJ, Chen GQ, et al. Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries.Med Hypotheses 2007;69(6):1234-1237.
[68]Li J, Sun CR, Zhang H,et al. Induction of functional recovery by co-transplantation of neural stem cells and Schwann cells in a rat spinal cord contusion injury model. Biomed Environ Sci 2007;20(3):242-249.
[69]Moviglia GA,Varela G,Brizuela JA,et al.Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.Spinal Cord.2009 Feb 17.[Epub ahead of print]PMID:19223861
[70]Yoon SH,Shim YS,Park YH,Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor:Phase Ⅰ/Ⅱ clinical trial.Stem Cells.2007Aug;25(8):2066-73.Epub 2007 Apr 26.PMID:17464087
[71]李长德,杨建华,刘铮,李东平.骨髓单个核细胞移植治疗急性脊髓损伤[J].中国组织工程研究与临床康复,2008,8(8):1431-1434.
[72]Shi E,Kazui T,Jiang X,et al.Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord.Ann Thorac Surg.2007 Apr;83(4):1484-1490.
[73]Padilla L,Kr(o|¨)tzsch E,De La Garza AS,et al.Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels:results from a canine ischemic hindlimb model.Microsurgery.2007;27(2):91-7.PMID:17186521
[74]Fernandes M,Valente SG,Fernandes MJ,et al.Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion.J Neurosci Methods.2008 May 15;170(1):16-24.Epub 2007Dec 23.PMID:18241927
[2]Barry FP.Biology and clinical applications of mesenchymal stem cells.Birth Defects Res C Embryo Today 2003;69(3):250-256.
[3]Horner PJ,Gage FH.Regenerating the damaged central nervous system.Nature 2000;407:963-970.PMID:11069169
[4]Weiss S,Dunne C,Hewson J,et al.Multipotent CNS stem cells are present in the adult mammalian spinal cord.J NeuroSci 1996;16:7599-7609.PMID:8922416
[5]Shihabuddin LS,Ray J,Gage FH.FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord.Exp Neurol 1997;148:577-586.PMID:9417834
[6]Horky LL,Galimi F,Gage FH,et al.Fate of endogenous stem/progenitor cells following spinal cord injury.J Comp Neurol.2006 Oct 1;498(4):525-38.PMID:16874803
[7]Alonso G.NG2 proteoglycan-expressing cells of the adult rat brain:possible involvement in the formation of glial scar astrocytes following stab wound.Gila 2005;49:318-338.PMID:15494983
[8]Chernykh ER,Stupak VV,Muradov GM,et al.Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients.Bull Exp Biol Med.2007 Apr;143(4):543-7.PMID:18214319
[9]Callera F,do Nascimento RX.Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury:a preliminary safety study.Exp Hematol.2006 Feb;34(2):130-131.PMID:16459180
[10]Deda H,Inci MC,K(u|¨)rekci AE,et al.Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up.Cytotherapy.2008;10(6):565-74.PMID:18615345
[11]崔贵祥,李义召,高华,等.自体骨髓间充质干细胞治疗神经系统疾病初步研究.中国康复理论与实践,2006,12(3):242-245.
[12]谢遵伟,崔贵祥,李义召,等.自体骨髓间充质干细胞治疗脊髓损伤疗效观察.中国组织工程研究与临床康复,2007,11(7):1277-1279.
[13]Sykova E,Homola A,Mazanec R,et al.Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.Cell Transplant 2006;15(8-9):675-687.PMID:17269439
[14]Saito F,Nakatani T,Iwase M,et al.Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation:the first clinical trial case report.J Trauma.2008 Jan;64(1):53-59.PMID:18188099
[15]Callera F,de Melo CM.Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury:CD34+ cells' migration into the injured site.Stem Cells Dev 2007;16(3):461-466.PMID:17610376
[16]Moviglia GA,Varela G,Brizuela JA,et al.Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.Spinal Cord. 2009 Feb 17. [Epub ahead of print] PMID: 19223861
[17]Yoon SH, Shim YS, Park YH, Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial.Stem Cells. 2007 Aug;25(8):2066-73. Epub 2007 Apr 26. PMID: 17464087
[18]Hamano K, Nishida M, Hirata K,et al.Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001 Sep;65(9):845-7.
[19]Strauer BE, Brehm M, Zeus T,et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr. 2001 Aug 24;126(34-35):932-8.
[20]Strauer BE, Brehm M, Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002 Oct 8;106(15):1913-8.
[21]Wollert KC, Meyer GP, Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.Lancet. 2004 Jul 10-16;364(9429):141-8.
[22]Carvalho KA, Cunha RC, Vialle EN, et al. Functional outcome of bone marrow stem cells (CD45~+/CD34) after cell therapy in acute spinal cord injury: in exercise training and sedentary rats. Transplant Proc. 2008 Apr;40(3):847-849.
[23]Carvalho KA, Vialle EN, Moreira GH.et al. Functional outcome of bone marrow stem cells (CD45~+/CD34~-) after cell therapy in chronic spinal cord injury in Wistar rats.Transplant Proc. 2008 Apr;40(3):845-846.
[24]Modo M, Stroemer RP, Tang E, et al. Effects of implantation site of stem cell grafts on behaveoval recovery from stroke damage. Stroke 2002;33(9):2270-2278.
[25]Vaquero J, Zurita M, Oya S,et al. Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration? Neurosci Lett. 2006 May 1;398(1-2): 129-34.
[26]Dezawa M, Kanno H, Hoshino M, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest. 2004;113(12):1701-10.
[27]Sheth RN, Manzano G, Li X,et al. Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats. J Neurosurg Spine. 2008 Feb;8(2):153-62.
[28]Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine.2004 Sep 15;29(18):1971-1979.
[29]Ankeny DP, McTigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004 Nov;190(1):17-31.
[30]Yano S, Kuroda S, Lee JB, et al. In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.J Neurotrauma. 2005 Aug;22(8):907-18.PMID: 16083357
[31]Koda M, Okada S, Nakayama T, et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice.Neuroreport. 2005 Nov 7;16(16):1763-7.
[32]Yoshihara T, Ohta M, Itokazu Y.et al. Neuroprotective effect of bone marrow-derived mononuclear cells promoting functional recovery from spinal cord injury. J Neurotrauma. 2007 Jun;24(6): 1026-36.
[33]lsele NB, Lee HS, Landshamer S, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.Neurochem Int. 2007 Jan;50(1):243-50. Epub 2006 Oct 16. PMID: 17050038
[34] Dasari VR, Spomar DG, Cady C, et al. Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats. Neurochem Res 2007;32(12): 2080-2093. PMID: 17564836
[35]Yamasaki K, Setoguchi T, Takenouchi T, et al. Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury.Spine. 2009 Feb 15;34(4):323-7. PMID: 19182706
[36]Mahmood A, Lu D, Chopp M. Intravenous administration of marrow stromal cells (MSCs) increase the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 2004;21(1):33-39.
[37]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cells support extensive axonal growth at sotes of spinal cord injury.Exp Neurol. 2005;191(2):344-360.
[38]Neuhuber B, Timothy Himes B, Shumsky JS, et al. Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res. 2005 Feb 21;1035(1):73-85.
[39]Xiang S, Pan W, Kastin AJ. Strategies to creat a regenerating enviroment for the injured spinal cord. Curr Pharm Des,2005,11(10):1267-1277.
[40]Lu P, Jones LL, Tuszynski MH. Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol. 2007 Jan;203(1):8-21.
[41]Tao H,Rao R,Ma DD.Cytokine-induced stable neuronal differentiation of human bone marrow mesenchymal stem cells in a serum/feeder cell-free condition.Dev Growth Differ 2005;47(6):423-433.
[42]Zhang J,Li Y,Chopp M.Exprssion of insulin-like growth factor 1and receptor in ischemic rats treated with human marrow stromal cells.Brain Res 2004;1030(1):19-27.
[43]李长德,杨建华,刘铮,李东平.骨髓单个核细胞移植治疗急性脊髓损伤[J].中国组织工程研究与临床康复,2008,8(8):1431-1434.
[44]Shi E,Kazui T,Jiang X,et aI.Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord.Ann Thorac Surg.2007 Apr;83(4):1484-1490.
[45]Fan L,DU F,Cheng BC,et al.Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques.Chin J Traumatol.2008 Apr;11(2):94-7.PMID:18377712
[1]Alonso G.NG2 proteoglycan-expressing cells of the adult rat brain:possible involvement in the formation of glial scar astrocytes following stab wound.Glia 2005;49:318-338.PMID:15494983
[2]Garbossa D,Fontanella M,Fronda C,et al.New Strategies for repairing the injured spinal cord:the role of stem cells.Neurol Res 2006;28(5):500-504.
[3]Barry FP.Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 2003;69(3):250-256.
[4]Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature 2000; 407: 963-970. PMID: 11069169
[5]Weiss S, Dunne C, Hewson J, et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord. J NeuroSci 1996;16:7599-7609. PMID: 8922416
[6]Shihabuddin LS, Ray J, Gage FH. FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp Neurol 1997;148:577-586. PMID: 9417834
[7]Horky LL, Galimi F, Gage FH, et al. Fate of endogenous stem/progenitor cells following spinal cord injury.J Comp Neurol.2006 Oct 1;498 (4): 525-38. PMID: 16874803
[8]Sigurjonsson OE, Perreault MC, Egeland T, et al. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord.Proc NatI Acad Sci U S A.2005 Apr 5; 102 (14): 5227-32. Epub 2005 Mar 24. PMID: 15790679
[9]Wright KT, Masri WE, Osman A, et al. The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury:implications for future cell transplantation therapy.Spinal Cord. 2008 Dec;46(12):811-7. Epub 2008 Jun 17. PMID: 18560372
[10]Kamishina H, Cheeseman JA, Clemmons RM. Nestin-positive spheres derived from canine bone marrow stromal cells generate cells with early neuronal and glial phenotypic characteristics.In Vitro Cell Dev Biol Anim. 2008 May-Jun;44(5-6): 140-4. Epub 2008 Apr 9. PMID: 18398665
[11]Neuhuber B, Swanger SA, Howard L, et al. Effects of plating density and culture time on bone marrow stromal cell characteristics.Exp Hematol. 2008 May 19. [Epub ahead of print] PMID: 18495329
[12]李栋,沈柏均,侯怀水,等.兔骨髓间充质干细胞的生物学牲及其 对不同生长因子的反应.中国实验血液学杂志[J].2006,14(5):964-968.
[13]王忠 高毅 汪艳,等.人骨髓间充质干细胞的分离培养与鉴定.中华神经医学杂志[J].2006,5(10):973-977.
[14]王红梅,郭光华.骨髓间充质干细胞的生物学特性.江西医学院学报[J].2006,46(5):169-172.
[15]David CC,Reiner C,Carla M et al.Rapid expansion of fecycling stem cells in cultrues of plastic adherent cells from human bone marrow[J].Proc Natl Acad Sci USA,2000,97(7):3213-3218.
[16]Pittenger F,Mackay A,Beck S et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284143-284147.
[17]Bruder SP,Jaiswal N,Haynesworth SE.Growth kinetics,self renewal,and the osteogenic potrential of purified human mesenchymal stem cells during extensive subculativation and following cryopreservation[J].J Cell Biochem,1997,64:278-294.
[18]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.
[19]Anselme K,Noel B,Flautre B et aI.Association of porous hydroxyapapite and bone marrow cells for bone regeneration[J].Bone,1999,25(2):51-54.
[20]Conget PA,Minguell JJ.Phenotypical and functional properties of huamn bone marrow mesenchymal progenitor cells[J].J Cell Physiol,1999,181(1):67-73.
[21]程朝辉,郑启新,郭晓东,等.不同诱导剂对骨髓间充质干细胞向神经元分化的影响[J].中国骨与关节损伤杂志,2007,22(2):119-121.
[22]Zhang W,Zeng YS,Zhang XB,et al.Combination of adenoviral vector-mediated neurotrophin-3 gene transfer and retinoic acid promotes adult bone marrow cells to differentiate into neuronal phenotypes.NeuroSci Lett.2006 Nov 13;408(2):98-103.Epub 2006 Sep 25.PMID:16996685
[23]Rooney GE,Moran C,McMahon SS,et al.Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid(PLGA) substrate.Tissue Eng PartA.2008 May;14(5):681-90.PMID:18402551
[24]Bi XB,Deng YB,Gan DH,et al.Salvianolic acid B promotes survival of transplanted mesenchymal stem cells in spinal cord-injured rats.Acta Pharmacol Sin.2008 Feb;29(2):169-76.PMID:18215345
[25]董立华,王勇,陆长青,等.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞的研究[J].四川大学学报:医学版,2007,38(3):417-420.
[26]王明宁,林洪,胡琳,等.香丹注射液对大鼠骨髓间充质干细胞的增殖作用[J].华西药学杂志,2007,22(3):304-305.
[27]赵汉宁.鹿茸精诱导大鼠骨髓间充质干细胞分化为神经元样细胞[J].现代医药卫生,2007,23(1):3-5.
[28]Carvalho KA,Vialle EN,Moreira GH,et aI.Functional outcome of bone marrow stem cells(CD45(+)/CD34(-)) after cell therapy in chronic spinal cord injury in Wistar rats.Transplant Proc.2008Apr;40(3):845-6.PMID:18455033
[29]Urdzikova L,Jendelova P,Glogarova K,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.PMID:16958589
[30]Chernykh ER,Stupak W,Muradov GM,et al.Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients.Bull Exp Biol Med.2007 Apr;143(4):543-7.PMID:18214319
[31]Callera F,do Nascimento RX.Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury:a preliminary safety study.Exp Hematol.2006 Feb;34(2):130-131.PMID:16459180
[32]Koshizuka S,Okada S,Okawa A,et al.Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice.J Neuropathol Exp Neurol.2004 Jan;63(1):64-72.PMID:14748562
[33]Koda M,Okada S,Nakayama T,et al.Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice.Neuroreport.2005Nov 7;16(16):1763-7.PMID:16237323
[34]Deda H,Inci MC,K(u|¨)rekci AE,et al.Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up.Cytotherapy.2008;10(6):565-74.PMID:18615345
[35]Satake K,Lou J,Lenke LG.Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue.Spine.2004 Sep 15;29(18):1971-9.PMID:15371697
[36]Sheth RN,Manzano G,Li X,et al.Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats.J Neurosurg Spine.2008 Feb;8(2):153-62.PMID:18248287
[37]吴佳奇,冯大雄,杨天府,等.骨髓间充质干细胞经蛛网膜下腔移植治疗大鼠脊髓损伤及其对T细胞亚群影响的研究[J].中国修复重建外科杂志,2007,21(5):492-496
[38]Deng YB,Liu XG,Liu ZG,et al.Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery:evidence from a study in rhesus monkeys.Cytotherapy.2006;8(3):210-4.PMID:16793730
[39]崔贵祥,李义召,高华,等.自体骨髓间充质干细胞治疗神经系统疾病初步研究.中国康复理论与实践,2006,12(3):242-245.
[40]谢遵伟,崔贵祥,李义召,等.自体骨髓间充质干细胞治疗脊髓损伤疗效观察.中国组织工程研究与临床康复,2007,11(7):1277-1279.
[41]Bakshi A,Barshinger AL,Swanger SA,et al.Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion:a novel method for minimally invasive cell transplantation.J Neurotraumao 2006 Jan;23(1):55-65.PMID:16430372
[42]Sykova E,Homola A,Mazanec R,et al.Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.Cell Transplant 2006;15(8-9):675-687.PMID:17269439
[43]Saito F,Nakatani T,Iwase M,et al.Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation:the first clinical trial case report.J Trauma.2008 Jan;64(1):53-59.PMID:18188099
[44]Koda M,Kamada T,Hashimoto M,et al.Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord.Eur Spine J.2007 Dec;16(12):2206-2214.Epub 2007Sep 21.PMID:17885772
[45]Ronsyn MW,Daans J,Spaepen G,et al.Plasmid-based genetic modification of human bone marrow-derived stromal cells:analysis of cell survival and transgene expression after transplantation in rat spinal cord.BMC Biotechnol.2007 Dec 14;7:90.
[46]Fan L,DU F,Cheng BC,et al.Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques.Chin J Traumatol.2008 Apr;11(2):94-7.PMID:18377712
[47]Yano S,Kuroda S,Lee JB,et al.In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.J Neurotrauma.2005 Aug;22(8):907-18.PMID:16083357
[48]白金柱,刘忠军,丁为民,等.多巴胺D_2受体正电子发射计算机短程显像示踪兔脊髓内移植的神经前体细胞[J].中华医学杂志,2006,86(29):2060-2064
[49]Sykova E,Jendelova P.In vivo tracking of stem cells in brain and spinal cord injury.Prog Brain Res.2007;161:367-83.PMID:17618991
[50]Callera F,de Melo CM.Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury:CD34+ cells' migration into the injured site.Stem Cells Dev 2007;16(3):461-466.PMID:17610376
[51]Yoshihara T,Ohta M,Itokazu Y,et al.Neuroprotective effect of bone marrow-derived mononuclear cells promoting functional recovery from spinal cord injury.J Neurotrauma.2007 Jun;24(6):1026-36.PMID:17600518
[52]Yano S,Kuroda S,Shichinohe H,et al.Bone marrow stromal cell transplantation preserves gammaamino- butyric acid receptor function in the injured spinal cord.J Neurotrauma.2006Nov;23(11):1682-92.PMID:17115913
[53]Rouleau P, Ung RV, Lapointe NP, et al. Hormonal and immunological changes in mice after spinal cord injury.J Neurotrauma. 2007 Feb;24(2):367-78. PMID: 17376000
[54]lversen PO, Hjeltnes N, Holm B, et al. Depressed immunity and impaired proliferation of hematopoietic progenitor cells in patients with complete spinal cord injury.Blood. 2000 Sep 15;96(6):2081-3.PMID: 10979951
[55]Fleming JC, Norenberg MD, Ramsay DA.et al. The cellular inflammatory response in human spinal cords after injury.Brain.2006 Dec;129(Pt 12):3249-69. Epub 2006 Oct 28. PMID:17071951
[56]Moviglia GA, Varela G, Gaeta CA.Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells.Cytotherapy. 2006;8(3):196-201. PMID: 16793728
[57]Yamasaki K, Setoguchi T, Takenouchi T, et al. Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury.Spine. 2009 Feb 15;34(4):323-7. PMID: 19182706
[58]lsele NB, Lee HS, Landshamer S, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.Neurochem Int. 2007 Jan;50(1):243-50. Epub 2006 Oct 16. PMID: 17050038
[59]Dasari VR, Spomar DG, Cady C, et al. Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats. Neurochem Res 2007;32(12): 2080-2093. PMID: 17564836
[60]Sasaki M, Honmou O, Akiyama Y, et al. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons.Glia. 2001 Jul;35(1):26-34. PMID: 11424189
[61]Akiyama Y, Radtke C, Honmou O, Remyelination of the spinal cord following intravenous delivery of bone marrow cells.Glia. 2002 Sep;39(3):229-36. PMID: 12203389
[62]Cao Q, Ding P, Lu J, et al. 2\ 3'-Cyclic nucleotide 3'-phosphodiesterase cells derived from transplanted marrow stromal cells and host tissue contribute to perineurial compartment formation in injured rat spinal cord.J NeuroSci Res. 2007 Jan;85(1):116-30. PMID: 17061258
[63]Blesch A, Tuszynski MH. Transient growth factor delivery sustains regenerated axons after spinal cord injury. J NeuroSci 2007,27(39):10535-10545.
[64]Lu P, Jones LL, Tuszynski MH. Axon regeneration through scars and into sites of chronic spinal cord injury.Exp Neurol. 2007 Jan;203(1):8-21. Epub 2006 Oct2. PMID: 17014846
[65]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury.Exp Neurol.2005 Feb;191(2):344-60. PMID: 15649491
[66]Kim KN, Oh SH, Lee KH, et al. Effect of human mesenchymal stem cell transplantation combined with growth factor infusion in the repair of injured spinal cord. Acta Neurochir Suppl 2006;99:133-136.
[67]Ao Q, Wang AJ, Chen GQ, et al. Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries.Med Hypotheses 2007;69(6):1234-1237.
[68]Li J, Sun CR, Zhang H,et al. Induction of functional recovery by co-transplantation of neural stem cells and Schwann cells in a rat spinal cord contusion injury model. Biomed Environ Sci 2007;20(3):242-249.
[69]Moviglia GA,Varela G,Brizuela JA,et al.Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.Spinal Cord.2009 Feb 17.[Epub ahead of print]PMID:19223861
[70]Yoon SH,Shim YS,Park YH,Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor:Phase Ⅰ/Ⅱ clinical trial.Stem Cells.2007Aug;25(8):2066-73.Epub 2007 Apr 26.PMID:17464087
[71]李长德,杨建华,刘铮,李东平.骨髓单个核细胞移植治疗急性脊髓损伤[J].中国组织工程研究与临床康复,2008,8(8):1431-1434.
[72]Shi E,Kazui T,Jiang X,et al.Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord.Ann Thorac Surg.2007 Apr;83(4):1484-1490.
[73]Padilla L,Kr(o|¨)tzsch E,De La Garza AS,et al.Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels:results from a canine ischemic hindlimb model.Microsurgery.2007;27(2):91-7.PMID:17186521
[74]Fernandes M,Valente SG,Fernandes MJ,et al.Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion.J Neurosci Methods.2008 May 15;170(1):16-24.Epub 2007Dec 23.PMID:18241927