Autologous Transplantation of Stem Cells for Diabetic Peripheral Neuropathy: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Fang ¹ , GAO Wei ² ,  RAN Xingwu ³

1. Sichuan Provincial Transportation Department Highway Bureau Hospital, Chengdu 610097, China;2. West China Clinical Medicine College, Sichuan University, Chengdu 610041, China;3. Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

RAN Xingwu, Email: ranxingwu@yahoo.com.cn

Keywords：

Diabetic peripheral neuropathy; Autologous bone marrow stem cell; Cell implantation; Systematic review; Meta-analysis; Randomized clinical trial

DOI：

10.7507/1672-2531.20130187

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To systematically review the effectiveness and safety of autologous implantation of stem cells for diabetic peripheral neuropathy (DPN).
Methods 　Randomized controlled trials on relevant studies were retrieved in databases including CBM (1978-2011.6), CNKI (1979-2011.6), MEDLINE (1950-2011.6), PubMed (1950-2011.6), EMbase (1970-2011.6) and The Cochrane Library (Issue 3, 2011). References of the included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assess the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software.
Results 　Four RCTs involving 68 patients (136 limbs) were included, most of which were low in methodological quality. The results of meta-analysis indicated that, autologous stem cell therapy improved or even eliminated DPN symptoms including pain, numbness, and cold sensation in the limbs, intermittent limping, and rest pain. Compared with the routine therapy, autologous stem cell therapy improved tibial sensory nerve conduction velocity (MD=5.75, 95%CI 3.86 to 7.64, P lt;0.000 01), tibial motor nerve conduction velocity (MD=4.04, 95%CI 0.90 to 7.18, P=0.001), sural sensory nerve conduction velocity (MD=7.47, 95%CI 4.00 to 10.94, P lt;0.000 1), and sural motor nerve conduction velocity (MD=3.38, 95%CI 0.07 to 7.58, P=0.05), with no adverse reaction reported.
Conclusion 　Current evidence shows that, autologous stem cell therapy is effective in treating DPN. Due to the lack of high quality studies, more high quality RCTs are needed to verify the above conclusion.

Citation： WANG Fang,GAO Wei,RAN Xingwu. Autologous Transplantation of Stem Cells for Diabetic Peripheral Neuropathy: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2013, 13(9): 1090-1095. doi: 10.7507/1672-2531.20130187 Copy

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2.	Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone marrow cells: a pilot study and a randomised controlled trial. Lancet, 2002, 360(9331): 427-435.
3.	谷涌泉, 张建, 齐立行, 等. 自体骨髓干细胞移植治疗下肢神经病变的效果: 3例讨论. 中国临床康复, 2005, 9(8): 46-48.
4.	Naruse K, Nakamura J. Therapeutic vasculogenesis using endothelial progenitor cells for treatment of diabetic neuropathies. Nippon Rinsho, 2005, 63(6): 622-626.
5.	Jeong JO, Kim MO, Kim H. Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation, 2009, 119(5): 699-708.
6.	Kim H, Park JS, Choi YJ, et al. Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy. Stem Cells, 2009, 27(7): 1686-1696.
7.	Naruse K, Nakamura J. Cell transplantation therapy for diabetic neuropathy. Nippon Rinsho, 2010, 68(9): 627-631.
8.	Nyman LR, Ford E, Powers AC, et al. Glucose dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab, 2010, 298(4): E807-E814.
9.	Umemura T, Soga J, Hidaka T, et al. Aging and hypertension are independent risk f actors for reduced number of circulating endothelial progenitor cells. Am J Hypertens, 2008, 21(11): 1203-1209.
10.	Martin D, Schoenen J, Delrée P, et al. Grafts of syngenic cultured, adult dorsal root ganglion-derived Schwann cells to the injured spinal cord of adult rats: preliminary morphological studies. Neurosci Lett, 1991, 124(1): 44-48.
11.	Cuevas P, Careeller F, Dujovny M, et al. Peripheral nerve regeneration by bone marrow stromal ceils. Neurol Res, 2002, 24(7): 634-638.
12.	Isner JM, Ropper A, Hirst K. VEGF gene transfer for diabetic neuropathy. Hum Gene Ther, 2001, 12(3): 1593-1594.
13.	Chen X, Katakowski M, Li Y, et al. Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: growth factor production. Neurosci Res, 2002, 69(5): 687-691.
14.	The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. Available from: http://www.cochrane.org/.htm.
15.	张慧芹, 刘阁玲, 俞芳, 等. 自体骨髓干细胞移植配合针灸治疗糖尿病周围神经病变患者24例双下肢神经电生理变化. 中国组织工程研究俞临床康复, 2007, 11(11): 2065-2067.
16.	张慧芹, 刘阁玲, 俞芳, 等. 自体骨髓干细胞移植对糖尿病周围神经电生理改变的影响.临床荟萃, 2007, 22(4): 263-264.
17.	胡增祥, 赵琪, 唐井钢, 等. 自体骨髓干细胞移植治疗糖尿病周围神经病变临床研究. 白求恩军医学院学报, 2010, 8(2): 102-103.
18.	Arima K, Katsuda Y, Takeshita Y, et al. Autologous transplantation of bone marrow mononuclear cells improved ischemic peripheral neuropathy in humans. J Am Coll Cardiol, 2010, 56(3): 238-239.
19.	张轶斌, 杨晓凤, 王红梅, 等. 自体外周血干细胞移植治疗下肢缺血性疾病术前行干细胞动员引发心脑血管危险因素的探讨. 临床内科杂志, 2005, 22(6): 422.
20.	吕柏南, 石晓明, 赵建辉, 等. 自体外周血干细胞移植治疗下肢动脉缺血术后淋巴瘤一例. 中华普通外科杂志, 2007, 22(10): 749.
21.	GREDE working group. Introduction of GREDE working groupEB/OL. 2000-01-01. Available from: http://www.gradeworkinggroup.org/.htm.

1. 朱禧星. 现代糖尿病学. 上海: 复旦大学出版社. 2001: 333-341.
2. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone marrow cells: a pilot study and a randomised controlled trial. Lancet, 2002, 360(9331): 427-435.
3. 谷涌泉, 张建, 齐立行, 等. 自体骨髓干细胞移植治疗下肢神经病变的效果: 3例讨论. 中国临床康复, 2005, 9(8): 46-48.
4. Naruse K, Nakamura J. Therapeutic vasculogenesis using endothelial progenitor cells for treatment of diabetic neuropathies. Nippon Rinsho, 2005, 63(6): 622-626.
5. Jeong JO, Kim MO, Kim H. Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation, 2009, 119(5): 699-708.
6. Kim H, Park JS, Choi YJ, et al. Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy. Stem Cells, 2009, 27(7): 1686-1696.
7. Naruse K, Nakamura J. Cell transplantation therapy for diabetic neuropathy. Nippon Rinsho, 2010, 68(9): 627-631.
8. Nyman LR, Ford E, Powers AC, et al. Glucose dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab, 2010, 298(4): E807-E814.
9. Umemura T, Soga J, Hidaka T, et al. Aging and hypertension are independent risk f actors for reduced number of circulating endothelial progenitor cells. Am J Hypertens, 2008, 21(11): 1203-1209.
10. Martin D, Schoenen J, Delrée P, et al. Grafts of syngenic cultured, adult dorsal root ganglion-derived Schwann cells to the injured spinal cord of adult rats: preliminary morphological studies. Neurosci Lett, 1991, 124(1): 44-48.
11. Cuevas P, Careeller F, Dujovny M, et al. Peripheral nerve regeneration by bone marrow stromal ceils. Neurol Res, 2002, 24(7): 634-638.
12. Isner JM, Ropper A, Hirst K. VEGF gene transfer for diabetic neuropathy. Hum Gene Ther, 2001, 12(3): 1593-1594.
13. Chen X, Katakowski M, Li Y, et al. Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: growth factor production. Neurosci Res, 2002, 69(5): 687-691.
14. The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. Available from: http://www.cochrane.org/.htm.
15. 张慧芹, 刘阁玲, 俞芳, 等. 自体骨髓干细胞移植配合针灸治疗糖尿病周围神经病变患者24例双下肢神经电生理变化. 中国组织工程研究俞临床康复, 2007, 11(11): 2065-2067.
16. 张慧芹, 刘阁玲, 俞芳, 等. 自体骨髓干细胞移植对糖尿病周围神经电生理改变的影响.临床荟萃, 2007, 22(4): 263-264.
17. 胡增祥, 赵琪, 唐井钢, 等. 自体骨髓干细胞移植治疗糖尿病周围神经病变临床研究. 白求恩军医学院学报, 2010, 8(2): 102-103.
18. Arima K, Katsuda Y, Takeshita Y, et al. Autologous transplantation of bone marrow mononuclear cells improved ischemic peripheral neuropathy in humans. J Am Coll Cardiol, 2010, 56(3): 238-239.
19. 张轶斌, 杨晓凤, 王红梅, 等. 自体外周血干细胞移植治疗下肢缺血性疾病术前行干细胞动员引发心脑血管危险因素的探讨. 临床内科杂志, 2005, 22(6): 422.
20. 吕柏南, 石晓明, 赵建辉, 等. 自体外周血干细胞移植治疗下肢动脉缺血术后淋巴瘤一例. 中华普通外科杂志, 2007, 22(10): 749.
21. GREDE working group. Introduction of GREDE working groupEB/OL. 2000-01-01. Available from: http://www.gradeworkinggroup.org/.htm.

Chinese Journal of Evidence-Based Medicine

Autologous Transplantation of Stem Cells for Diabetic Peripheral Neuropathy: A Systematic Review

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