Efficacy and safety of autologous bone marrow mesenchymal stem cells transplantation for spinal cord injury: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Qian ^1,2 ^# , HUANG Guoxin ³ ^# , ZHANG Huiting ³ , SHI Ye ³ , LIU Chufan ³ , Pradhananga Manish ¹ , AI Jinwei ^1,2,3 ,  PEI Bin ^1,2,3

1. Department of Plastic Surgery, the first People’s Hospital of Xiangyang, Hubei University of Medicine, Xiangyang, 442000, P.R.China;
2. Research Office of Plastic Surgery and Orthopedics, the first People’s Hospital of Xiangyang, Hubei University of Medicine, Xiangyang, 442000, P.R.China;
3. Evidence-Based Medicine Center, the first People’s Hospital of Xiangyang, Hubei University of Medicine, Xiangyang, 442000, P.R.China;

Corresponding author：

PEI Bin, Email: xyxzyxzx@163.com

Keywords：

Spinal cord injury; Bone marrow mesenchymal stem cells; Rehabilitation therapy; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.201707018

Video：

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ObjectivesTo systematically review the safety and efficacy of autologous bone marrow mesenchymal stem cells (BMSCs) transplantation for spinal cord injury (SCI) patients.MethodsPubMed, The Cochrane Library, EMbase, CNKI, CBM, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) and clinical controlled trials (CCTs) of autologous BMSCs transplantation for SCI patients from inception to June 8^th, 2017. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software.ResultsA total of 16 studies involving 954 SCI patients were included. The results of meta-analysis showed that: BMSCs could significantly increase the patients’ ASIA motor score (MD=6.91, 95%CI 3.95 to 9.87, P<0.000 01), ASIA light-tough score (MD=11.79, 95%CI 6.66 to 16.39,P<0.000 01), ASIA pain score (MD=8.76, 95%CI 4.11 to 13.40,P=0.000 2), Barthel index score (MD=8.47, 95%CI 7.32 to 9.61, P<0.000 01). It could also improve the ASIA grade (OR=3.75, 95%CI 2.35 to 5.99,P<0.01), and decrease the bladder urine residue (MD=–23.32, 95%CI –46.27 to –0.37,P=0.05). The complications mainly included headache, low-grade fever, and so forth. No serious adverse event and abnormal tissue formation occurred.ConclusionAutologous BMSCs transplantation is a safe and effective therapy for SCI. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusion.

Citation： WANG Qian, HUANG Guoxin, ZHANG Huiting, SHI Ye, LIU Chufan, Pradhananga Manish, AI Jinwei, PEI Bin. Efficacy and safety of autologous bone marrow mesenchymal stem cells transplantation for spinal cord injury: a systematic review. Chinese Journal of Evidence-Based Medicine, 2018, 18(7): 683-692. doi: 10.7507/1672-2531.201707018 Copy

1.	Ikpeze TC, Mesfin A. Spinal cord injury in the geriatric population: risk factors, treatment options, and long-term management. Geriatr Orthop Surg Rehabil, 2017, 8(2): 115-118.
2.	Lee BB, Cripps RA, Fitzharris M, et al. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord, 2014, 52(2): 110-116.
3.	Rouanet C, Reges D, Rocha E, et al. Traumatic spinal cord injury: current concepts and treatment update. Arq Neuropsiquiatr, 2017, 75(6): 387-393.
4.	Goel A. Stem cell therapy in spinal cord injury: Hollow promise or promising science? J Craniovertebr Junction Spine, 2016, 7(2): 121-126.
5.	Chen YB, Jia QZ, Li DJ, et al. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation. Int J Clin Exp Med, 2015, 8(6): 9348-9354.
6.	Ryabov SI, Zvyagintseva MA, Pavlovich ER, et al. Efficiency of transplantation of human placental/umbilical blood cells to rats with severe spinal cord injury. Bull Exp Biol Med, 2014, 157(1): 85-88.
7.	Shih CH, Lacagnina M, Leuer-Bisciotti K, et al. Astroglial-derived periostin promotes axonal regeneration after spinal cord injury. J Neurosci, 2014, 34(7): 2438-2443.
8.	Bryukhovetskiy AS, Bryukhovetskiy IS. Effectiveness of repeated transplantations of hematopoietic stem cells in spinal cord injury. World J Transplant, 2015, 5(3): 110-128.
9.	Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med, 2014, 12(1): 253.
10.	Moher D, Liberati A, Tetzlaff J, et al. Reprint-preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther, 2009, 89(9): 873-880.
11.	Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
12.	曾宪涛, 庄丽萍, 杨宗国, 等. Meta分析系列之七: 非随机实验性研究、诊断性试验及动物实验的质量评价工具. 中国循证心血管医学杂志, 2012, 4(6): 496-499.
13.	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, 143(4): 543-547.
14.	El-Kheir WA, Gabr H, Awad MR, et al. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant, 2014, 23(6): 729-745.
15.	Kishk NA, Gabr H, Hamdy S, et al. Case control series of intrathecal autologous bone marrowal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair, 2010, 24(8): 702-708.
16.	Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, et al. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg, 2012, 114(7): 935-939.
17.	Shin JC, Kim KN, Yoo J, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast, 2015, 2015(5): 1-22.
18.	Yoon S H, Shim YS, Park YH, et al. 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, 25(8): 2066-2073.
19.	Abdelaziz OS, Marie A, Abbas M, et al. Feasibility, safety, and efficacy of directly transplanting autologous adult bone marrow stem cells in patients with chronic traumatic dorsal cord injury. Neurosrugery Quarterly, 2010, 20(3): 216-226.
20.	Dai GH, Liu X, Zhang Z, et al. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res, 2013, 1533(1): 73-79.
21.	张拓, 佟旭, 刘晨. 骨髓间充质干细胞对脉冲低剂量效率放射性脊髓损伤细胞修复作用的研究. 世界最新医学信息文摘, 2015, 5(100): 64-65.
22.	郭志松, 秦秉玉, 代荣钦, 等. 骨髓间充质干细胞治疗脊髓损伤的研究. 中华实验科学杂志, 2014, 31(11): 2605-2607.
23.	肖以磊, 朱建新, 李忠民, 等. 两种不同途径移植自体骨髓间充质干细胞治疗早期脊髓损伤疗效观察. 中国医师进修杂志, 2012, 35(14): 24-28.
24.	崔贵祥, 宋成忠, 李义召, 等. 自体骨髓单个核细胞治疗脊髓损伤的临床研究. 中国康复医学杂志, 2009, 24(4): 309-312.
25.	姜金豆, 步星耀, 程培训, 等. 自体骨髓干细胞联合辛伐他汀治疗脊髓损伤. 河南医学研究, 2010, 19(4): 434-437.
26.	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, 2007, 11(7): 1277-1279.
27.	肖以磊, 李忠民, 朱建新, 等. 自体骨髓间充质干细胞治疗早期脊髓损伤疗效观察. 中华生物医学工程杂志, 2014, 20(1): 7-11.
28.	郭晓鹤, 步星耀, 闫兆月, 等. 自体骨髓基质干细胞动员联合神经生长因子及综合康复治疗脊髓损伤. 中华神经医学杂志, 2013, 12(8): 833-837.
29.	Lu P. Stem cell transplantation for spinal cord injury repair. Prog Brain Res, 2017, 231: 1-32.
30.	Zhu T, Tang Q, Gao H, et al. Current status of cell-mediated regenerative therapies for human spinal cord injury. Neurosci Bull, 2014, 30(4): 671-682.
31.	Shroff G, Dhanda TJ, Shroff R. A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy. Am J Stem Cells, 2017, 6(1): 1-12.
32.	Sarasúa JG, López SP, Viejo MÁ, et al. Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury. J Spin Cord Med, 2013, 34(3): 301-307.
33.	Li Z, Guo GH, Wang GS, et al. Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Genet Mol Res, 2014, 13(3): 6083-6092.
34.	Dedeepiya VD, William JB, Parthiban JK, et al. The known-unknowns in spinal cord injury, with emphasis on cell-based therapies-a review with suggestive arenas for research. Expert Opin Biol Ther, 2014, 14(5): 617-634.
35.	Oh SK, Choi KH, Yoo JY, et al. A phase III clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery, 2016, 78(3): 436-447.
36.	Pal R, Gopinath C, Rao NM, et al. Functional recovery after transplantation of bone marrow-derived human mesenchymal stromal cells in a rat model of spinal cord injury. Cytotherapy, 2010, 12(6): 792-806.
37.	Alkabie S, Boileau AJ. The role of therapeutic hypothermia after traumatic spinal cord injury-a systematic review. World Neurosurg, 2016, 86: 432-449.

1. Ikpeze TC, Mesfin A. Spinal cord injury in the geriatric population: risk factors, treatment options, and long-term management. Geriatr Orthop Surg Rehabil, 2017, 8(2): 115-118.
2. Lee BB, Cripps RA, Fitzharris M, et al. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord, 2014, 52(2): 110-116.
3. Rouanet C, Reges D, Rocha E, et al. Traumatic spinal cord injury: current concepts and treatment update. Arq Neuropsiquiatr, 2017, 75(6): 387-393.
4. Goel A. Stem cell therapy in spinal cord injury: Hollow promise or promising science? J Craniovertebr Junction Spine, 2016, 7(2): 121-126.
5. Chen YB, Jia QZ, Li DJ, et al. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation. Int J Clin Exp Med, 2015, 8(6): 9348-9354.
6. Ryabov SI, Zvyagintseva MA, Pavlovich ER, et al. Efficiency of transplantation of human placental/umbilical blood cells to rats with severe spinal cord injury. Bull Exp Biol Med, 2014, 157(1): 85-88.
7. Shih CH, Lacagnina M, Leuer-Bisciotti K, et al. Astroglial-derived periostin promotes axonal regeneration after spinal cord injury. J Neurosci, 2014, 34(7): 2438-2443.
8. Bryukhovetskiy AS, Bryukhovetskiy IS. Effectiveness of repeated transplantations of hematopoietic stem cells in spinal cord injury. World J Transplant, 2015, 5(3): 110-128.
9. Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med, 2014, 12(1): 253.
10. Moher D, Liberati A, Tetzlaff J, et al. Reprint-preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther, 2009, 89(9): 873-880.
11. Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
12. 曾宪涛, 庄丽萍, 杨宗国, 等. Meta分析系列之七: 非随机实验性研究、诊断性试验及动物实验的质量评价工具. 中国循证心血管医学杂志, 2012, 4(6): 496-499.
13. 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, 143(4): 543-547.
14. El-Kheir WA, Gabr H, Awad MR, et al. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant, 2014, 23(6): 729-745.
15. Kishk NA, Gabr H, Hamdy S, et al. Case control series of intrathecal autologous bone marrowal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair, 2010, 24(8): 702-708.
16. Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, et al. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg, 2012, 114(7): 935-939.
17. Shin JC, Kim KN, Yoo J, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast, 2015, 2015(5): 1-22.
18. Yoon S H, Shim YS, Park YH, et al. 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, 25(8): 2066-2073.
19. Abdelaziz OS, Marie A, Abbas M, et al. Feasibility, safety, and efficacy of directly transplanting autologous adult bone marrow stem cells in patients with chronic traumatic dorsal cord injury. Neurosrugery Quarterly, 2010, 20(3): 216-226.
20. Dai GH, Liu X, Zhang Z, et al. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res, 2013, 1533(1): 73-79.
21. 张拓, 佟旭, 刘晨. 骨髓间充质干细胞对脉冲低剂量效率放射性脊髓损伤细胞修复作用的研究. 世界最新医学信息文摘, 2015, 5(100): 64-65.
22. 郭志松, 秦秉玉, 代荣钦, 等. 骨髓间充质干细胞治疗脊髓损伤的研究. 中华实验科学杂志, 2014, 31(11): 2605-2607.
23. 肖以磊, 朱建新, 李忠民, 等. 两种不同途径移植自体骨髓间充质干细胞治疗早期脊髓损伤疗效观察. 中国医师进修杂志, 2012, 35(14): 24-28.
24. 崔贵祥, 宋成忠, 李义召, 等. 自体骨髓单个核细胞治疗脊髓损伤的临床研究. 中国康复医学杂志, 2009, 24(4): 309-312.
25. 姜金豆, 步星耀, 程培训, 等. 自体骨髓干细胞联合辛伐他汀治疗脊髓损伤. 河南医学研究, 2010, 19(4): 434-437.
26. 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, 2007, 11(7): 1277-1279.
27. 肖以磊, 李忠民, 朱建新, 等. 自体骨髓间充质干细胞治疗早期脊髓损伤疗效观察. 中华生物医学工程杂志, 2014, 20(1): 7-11.
28. 郭晓鹤, 步星耀, 闫兆月, 等. 自体骨髓基质干细胞动员联合神经生长因子及综合康复治疗脊髓损伤. 中华神经医学杂志, 2013, 12(8): 833-837.
29. Lu P. Stem cell transplantation for spinal cord injury repair. Prog Brain Res, 2017, 231: 1-32.
30. Zhu T, Tang Q, Gao H, et al. Current status of cell-mediated regenerative therapies for human spinal cord injury. Neurosci Bull, 2014, 30(4): 671-682.
31. Shroff G, Dhanda TJ, Shroff R. A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy. Am J Stem Cells, 2017, 6(1): 1-12.
32. Sarasúa JG, López SP, Viejo MÁ, et al. Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury. J Spin Cord Med, 2013, 34(3): 301-307.
33. Li Z, Guo GH, Wang GS, et al. Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Genet Mol Res, 2014, 13(3): 6083-6092.
34. Dedeepiya VD, William JB, Parthiban JK, et al. The known-unknowns in spinal cord injury, with emphasis on cell-based therapies-a review with suggestive arenas for research. Expert Opin Biol Ther, 2014, 14(5): 617-634.
35. Oh SK, Choi KH, Yoo JY, et al. A phase III clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery, 2016, 78(3): 436-447.
36. Pal R, Gopinath C, Rao NM, et al. Functional recovery after transplantation of bone marrow-derived human mesenchymal stromal cells in a rat model of spinal cord injury. Cytotherapy, 2010, 12(6): 792-806.
37. Alkabie S, Boileau AJ. The role of therapeutic hypothermia after traumatic spinal cord injury-a systematic review. World Neurosurg, 2016, 86: 432-449.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of autologous bone marrow mesenchymal stem cells transplantation for spinal cord injury: a systematic review

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