Efficacy and Safety of Bone Mesenchymal Stem Cells Transplantation for Ischemic Stroke: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 LIUChao ,  WUHai-qin , YANPu , ZHAOJia-xin , GAOZhen , LIPeng , ZHANGMeng

Department of Neurology, the Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an 710004, China;

Corresponding author：

WUHai-qin, Email: eryuanwhq@126.com

Keywords：

Bone marrow mesenchymal stem cell; Transplantation; Ischemic stroke; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20150110

Video：

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Objective To systematically review the efficacy and safety of bone mesenchymal stem cells (BMSCs) transplantation for ischemic stroke. Methods We electronically searched PubMed, The Cochrane Library (Issue 12, 2014), EMbase, CBM, CNKI and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) of BMSCs transplantation for ischemic stroke. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 6 RCTs involving 332 patients were included. The results of meta-analysis showed that, the BMSCs transplantation group was superior to the routine treatment group with significant differences in the neurologic deficits score (NIHSS score)(MD=-2.09, 95%CI -2.88 to -1.29, P<0.000 01), motor function (Fugl-Meyer rating scale) (MD=15.25, 95%CI 13.51 to 16.99, P<0.000 01) and daily life ability (Barthel index) (MD=20.04, 95%CI 9.91 to 30.17, P=0.000 1) after 3 months treatment. Two trials reported the adverse events including fever and headache, but the patients relieved in a brief period. Conclusion Current evidence shows that BMSCs transplantation can improve the neurological deficits, motor function and daily life ability after ischemic stroke with less adverse effect. No serious adverse events are observed. However, more high quality studies are needed to confirm its effects for lowering rates of death and dependency of BMSC.

Citation： LIUChao, WUHai-qin, YANPu, ZHAOJia-xin, GAOZhen, LIPeng, ZHANGMeng. Efficacy and Safety of Bone Mesenchymal Stem Cells Transplantation for Ischemic Stroke: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2015, 15(6): 659-663. doi: 10.7507/1672-2531.20150110 Copy

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12.	孟宪国,朱士文,高华,等.自体骨髓间充质干细胞移植治疗脑梗死:6个月随访.中国组织工程研究与临床康复,2009,13(32):6374-6378.
13.	谢旭芳,刘诗英,金光华,等.自体骨髓间充质干细胞移植治疗脑梗死的临床分析.检验医学与临床,2014,(21):2955-2957.
14.	Friedenstein AJ,Petrakova KV,Kurolesova AI,et al.Heterotopic of bone marrow.Analysis of precursor cells for osteogenic and hematopoietic tissues.Transplantation,1968,6(2):230-247.
15.	Kopen GC,Prockop DJ,Phinney DG.Marrow stromal cells migrate throughout forebrain and cerebellum,and they differentiate into astrocytes after injection into neonatal mouse brains.Proc Natl Acad Sci USA,1999,96(19):10711-10716.
16.	Li Y,Chopp M,Chen J,et al.Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice.J Cereb Blood Flow Metab,2000,20(9):1311-1319.
17.	Mochizuki N,Moriyama Y,Takagi N,et al.Intravenous injection of neural progenitor cells improves cerebral ischemia-induced learning dysfunction.Biol Pharm Bull,2011,34(2):260-265.
18.	Rossini PM,Dal Forno G.Neuronal post-stroke plasticity in the adult.Restor Neurol Neurosci,2004,22(3-5):193-206.
19.	Iihoshi S,Honmou O,Houkin K,et al.A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats.Brain Res,2004,1007(1-2):1-9.
20.	周红青,王德任,张灿飞,等.通心络胶囊治疗急性缺血性脑卒中疗效与安全性的系统评价.中国循证医学杂志,2013,13(7):844-851.
21.	吴波,刘鸣,张世洪.丹参类药物治疗急性缺血性脑卒中的系统评价.中国循证医学杂志,2005,5(2):101-105.

1. Leys D,Goldstein P.Primary emergencies:management of acute ischemic stroke.Bull Acad Natl Med,2012,196(4-5):909-925.
2. Adams HP Jr,del Zoppo G,Alberts MJ,et al.Guidelines for the early management of adults with ischemic stroke.Stroke,2007,38(5):1655-1711.
3. Rombouts WJC,Ploemacher RE.Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture.Leukemia,2003,17(1):160-170.
4. Woodbury D,Reynolds K,Black IB.Adult bone marrow stromal stem cells express germline,ectodermal,endodermal,and mesodermal genes prior to neurogenesis.Journal of Neuroscience Research,2002,69(6):908-917.
5. 中华医学会第四次脑血管病学术会议组.各类脑血管疾病诊断要点.中华神经科杂志,1996,29(6):379-380.
6. Hatano S.Experience from a multicentre stroke register:a preliminary report.Bull World Health Organ,1976,54(5):541-553.
7. 王丹,翟俊霞,牟振云,等.Meta分析中的异质性及其处理方法.中国循证医学杂志,2009,9(10):1115-1118.
8. Bang OY,Lee JS,Lee PH,et al.Autologous mesenchymal stem cell transplantation in stroke patients.Ann Neurol,2005,57(6):874-882.
9. 陈文斗,李江涛,张效北,等.骨髓间充质干细胞移植治疗脑梗死临床分析.吉林医学,2012,33(21):4522-4522.
10. 何振东.骨髓间充质干细胞移植改善脑梗死患者神经功能机制研究.亚太传统医药,2012,8(12):126-127.
11. 刘定华,韩伯军,洪珊珊,等.自体骨髓间充质神经干细胞移植治疗脑梗死的疗效观察.中华物理医学与康复杂志,2014,36(6):425-428.
12. 孟宪国,朱士文,高华,等.自体骨髓间充质干细胞移植治疗脑梗死:6个月随访.中国组织工程研究与临床康复,2009,13(32):6374-6378.
13. 谢旭芳,刘诗英,金光华,等.自体骨髓间充质干细胞移植治疗脑梗死的临床分析.检验医学与临床,2014,(21):2955-2957.
14. Friedenstein AJ,Petrakova KV,Kurolesova AI,et al.Heterotopic of bone marrow.Analysis of precursor cells for osteogenic and hematopoietic tissues.Transplantation,1968,6(2):230-247.
15. Kopen GC,Prockop DJ,Phinney DG.Marrow stromal cells migrate throughout forebrain and cerebellum,and they differentiate into astrocytes after injection into neonatal mouse brains.Proc Natl Acad Sci USA,1999,96(19):10711-10716.
16. Li Y,Chopp M,Chen J,et al.Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice.J Cereb Blood Flow Metab,2000,20(9):1311-1319.
17. Mochizuki N,Moriyama Y,Takagi N,et al.Intravenous injection of neural progenitor cells improves cerebral ischemia-induced learning dysfunction.Biol Pharm Bull,2011,34(2):260-265.
18. Rossini PM,Dal Forno G.Neuronal post-stroke plasticity in the adult.Restor Neurol Neurosci,2004,22(3-5):193-206.
19. Iihoshi S,Honmou O,Houkin K,et al.A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats.Brain Res,2004,1007(1-2):1-9.
20. 周红青,王德任,张灿飞,等.通心络胶囊治疗急性缺血性脑卒中疗效与安全性的系统评价.中国循证医学杂志,2013,13(7):844-851.
21. 吴波,刘鸣,张世洪.丹参类药物治疗急性缺血性脑卒中的系统评价.中国循证医学杂志,2005,5(2):101-105.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Bone Mesenchymal Stem Cells Transplantation for Ischemic Stroke: A Systematic Review

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