Autologous bone marrow cell transplantation for patients with diabetic foot: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

GAO Haihui ^1,2 , LV Xiafei ³ , LI Sheyu ¹ , TIAN Haoming ¹ ,  RAN Xingwu ¹

1. Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, 610041, P.R.China;
2. West China School of Medicine, Sichuan University, Chengdu, 610041, P.R.China;
3. Department of Radiology, West China Hospital of Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

RAN Xingwu, Email: ranxingwu@163.com

Keywords：

Diabetic foot; Autologous bone marrow mononuclear cell transplantation; Randomized controlled trial; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.201708010

Video：

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ObjectivesTo systematically review the efficacy and safety of autologous bone marrow cells therapy for patients with diabetic foot. GRADE system was used to evaluate the evidence quality of outcomes.MethodsWe searched databases including PubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI for randomized controlled trials (RCTs) about bone marrow cell transplantation in patients with diabetic foot from inception to February 28^th 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed using RevMan 5.3 software. The evidence quality was evaluated by using GRADE profiler 3.6 software.ResultsFour RCTs were included. Meta-analysis showed that the bone marrow cell transplantation could decrease the rate of amputation (RR=0.08, 95%CI 0.00 to 1.32, P=0.08) and rest pain score (MD=–1.89, 95%CI –2.24 to –1.55, P<0.000 01), increase the rate of ameliorate ulcer healing (RR=2.01, 95%CI 1.45 to 2.79,P<0.000 1) and the quantity of new collateral vessels (MD=1.33, 95%CI 0.60 to 2.05,P<0.000 3). Besides, bone marrow cell transplantation could improve ankle-brachial index (MD=0.16, 95%CI 0.10 to 0.22,P<0.000 01) and transcutaneous arterial oxygen tension (MD=18.81, 95%CI 16.06 to 21.57,P<0.000 01). No adverse event was reported for all included studies. The qualities of evidence for all outcomes were rated as "low" to "very low".ConclusionBased on the current evidence, autologous bone marrow cells transplantation therapy has a certain effect and it is safe for patients with diabetic foot. However, due to the limited quantity and quality of included studies, the above conclusions are still needed more multicenter clinical trials with large sample size to confirm.

Citation： GAO Haihui, LV Xiafei, LI Sheyu, TIAN Haoming, RAN Xingwu. Autologous bone marrow cell transplantation for patients with diabetic foot: a systematic review. Chinese Journal of Evidence-Based Medicine, 2018, 18(2): 185-191. doi: 10.7507/1672-2531.201708010 Copy

1.	李舍予, 李芸, 周方励, 等. 四川大学华西医院内分泌代谢科 2011～2012 年住院患者疾病构成与费用调查. 中国循证医学杂志, 2014, 14(1): 25-29.
2.	李舍予, 李芸, 周方励, 等. 四川大学华西医院内分泌代谢科 2011 年糖尿病住院患者费用情况调查. 中国循证医学杂志, 2013, 13(10): 1180-1184.
3.	周海龙, 杨晓妍, 潘晓平, 等. 中国人群糖尿病疾病负担的系统评价. 中国循证医学杂志, 2014(12): 1442-1449.
4.	侯清涛, 李芸, 李舍予, 等. 全球糖尿病疾病负担现状. 中国糖尿病杂志, 2016, 24(1): 92-96.
5.	管珩, 刘志民, 李光伟, 等. 50 岁以上糖尿病人群周围动脉闭塞性疾病相关因素分析. 中华医学杂志, 2007, 87(1): 23-27.
6.	侯宇颖, 张志刚, 张珺, 等. 九种常用敷料治疗糖尿病足效果的网状 Meta 分析. 中国循证医学杂志, 2016, 16(11): 1291-1297.
7.	李永恒, 何利平, 冉兴无, 等. 华西医院住院糖尿病足的流行率及临床疗效. 西部医学, 2011, 23(7): 1228-1232.
8.	中国医疗保健国际交流促进会糖尿病足病分会. 中国糖尿病足诊治指南. 中华医学杂志, 2017, 97(4): 251-258.
9.	王芳, 高伟, 冉兴无. 自体骨髓干细胞移植治疗糖尿病周围神经病变的系统评价. 中国循证医学杂志, 2013, 13(9): 1090-1095.
10.	刘超, 吴海琴, 严璞, 等. 骨髓间充质干细胞移植治疗缺血性脑卒中疗效和安全性的 Meta 分析. 中国循证医学杂志, 2015(6): 659-663.
11.	杨柳, 唐其柱, 郭毅. 骨髓干细胞移植治疗扩张性心肌病疗效及安全性的系统评价. 中国循证医学杂志, 2015(2): 194-200.
12.	谷涌泉, 郭连瑞, 张建, 等. 自体骨髓干细胞移植治疗严重下肢缺血 1 例. 中国实用外科杂志, 2003, 19(11): 687-688.
13.	Benoit E, O'Donnell TF Jr, Iafrati MD, et al. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design. J Transl Med, 2011, 9(1): 165.
14.	Dubský M, Jirkovská A, Bem R, et al. Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia. Cytotherapy, 2014, 16(12): 1733-1738.
15.	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.
16.	Bartsch T, Brehm M, Zeus T, et al. Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (The TAM-PAD Study). Clin Res Cardiol, 2007, 96(12): 891-899.
17.	Sprengers RW, Lips DJ, Moll FL, et al. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg, 2008, 247(3): 411-420.
18.	Matoba S, Tatsumi T, Murohara T, et al. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (therapeutic angiogenesis by cell transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J, 2008, 156(5): 1010-1018.
19.	Kirana S, Stratmann B, Prante C, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract, 2012, 66(4): 384-393.
20.	Dubsky M, Jirkovska A, Bem R, et al. Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment. Diabetes Metab Res Rev, 2013, 29(5): 369-376.
21.	Iwase T, Nagaya N, Fujii T, et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res, 2005, 66(3): 543-551.
22.	Ishikane S, Ohnishi S, Yamahara K, et al. Allogeneic injection of fetal membrane-derived mesenchymal stem cells induces therapeutic angiogenesis in a rat model of hind limb ischemia. Stem Cells, 2008, 26(10): 2625-2633.
23.	Dash NR, Dash SN, Routray P, et al. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res, 2009, 12(5): 359-366.
24.	The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Available at: http://www.cochrane.org/.
25.	Lu D, Chen B, Liang Z, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract, 2011; 92(1): 26-36.
26.	张忠, 刘文申, 赵秀兰. 自体骨髓干细胞移植治疗糖尿病足溃疡. 实用临床医学, 2007, 8(8): 58-60.
27.	陈兵, 陆德宾, 梁自文, 等. 自体骨髓间充质干细胞体外扩增后移植治疗糖尿病足. 中国组织工程研究与临床康复, 2009, 13(32): 6227-6230.
28.	甘宇, 李铁男, 于黎丽, 等. 自体骨髓干细胞移植配合中药治疗糖尿病足溃疡的疗效及其与血清 VEGF 水平关系的研究. 中国中西医结合皮肤性病学杂志, 2010, 9(4): 206-209.
29.	Koch TG, Heerkens T, Thomsen PD, et al. Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol, 2007, 7(1): 1-9.
30.	王晶, 周敏, 孟荔, 等. 两种分离人骨髓单个核细胞方法的比较. 实用医学杂志, 2009, 25(5): 725-726.
31.	郝洪波, 任思坡, 谢晓东. 密度梯度离心法分离骨髓单个核细胞方法的优化. 吉林医学, 2012, 33(35): 7619-7620.
32.	迟作华, 张洹, 陆琰. 人骨髓间充质干细胞分离方法的比较. 中国组织工程研究, 2006, 10(1): 20-22.
33.	蔡金宏, 林春博, 杨渊. 间充质干细胞分离方法的研究与进展. 中国组织工程研究, 2014, 18(45): 7375-7380.
34.	邢文, 庞爱明, 姚剑峰, 等. 直接铺种结合改良组织块培养法可有效分离人骨髓中的间充质干细胞. 中国实验血液学杂志, 2013, 21(2): 451-454.

1. 李舍予, 李芸, 周方励, 等. 四川大学华西医院内分泌代谢科 2011～2012 年住院患者疾病构成与费用调查. 中国循证医学杂志, 2014, 14(1): 25-29.
2. 李舍予, 李芸, 周方励, 等. 四川大学华西医院内分泌代谢科 2011 年糖尿病住院患者费用情况调查. 中国循证医学杂志, 2013, 13(10): 1180-1184.
3. 周海龙, 杨晓妍, 潘晓平, 等. 中国人群糖尿病疾病负担的系统评价. 中国循证医学杂志, 2014(12): 1442-1449.
4. 侯清涛, 李芸, 李舍予, 等. 全球糖尿病疾病负担现状. 中国糖尿病杂志, 2016, 24(1): 92-96.
5. 管珩, 刘志民, 李光伟, 等. 50 岁以上糖尿病人群周围动脉闭塞性疾病相关因素分析. 中华医学杂志, 2007, 87(1): 23-27.
6. 侯宇颖, 张志刚, 张珺, 等. 九种常用敷料治疗糖尿病足效果的网状 Meta 分析. 中国循证医学杂志, 2016, 16(11): 1291-1297.
7. 李永恒, 何利平, 冉兴无, 等. 华西医院住院糖尿病足的流行率及临床疗效. 西部医学, 2011, 23(7): 1228-1232.
8. 中国医疗保健国际交流促进会糖尿病足病分会. 中国糖尿病足诊治指南. 中华医学杂志, 2017, 97(4): 251-258.
9. 王芳, 高伟, 冉兴无. 自体骨髓干细胞移植治疗糖尿病周围神经病变的系统评价. 中国循证医学杂志, 2013, 13(9): 1090-1095.
10. 刘超, 吴海琴, 严璞, 等. 骨髓间充质干细胞移植治疗缺血性脑卒中疗效和安全性的 Meta 分析. 中国循证医学杂志, 2015(6): 659-663.
11. 杨柳, 唐其柱, 郭毅. 骨髓干细胞移植治疗扩张性心肌病疗效及安全性的系统评价. 中国循证医学杂志, 2015(2): 194-200.
12. 谷涌泉, 郭连瑞, 张建, 等. 自体骨髓干细胞移植治疗严重下肢缺血 1 例. 中国实用外科杂志, 2003, 19(11): 687-688.
13. Benoit E, O'Donnell TF Jr, Iafrati MD, et al. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design. J Transl Med, 2011, 9(1): 165.
14. Dubský M, Jirkovská A, Bem R, et al. Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia. Cytotherapy, 2014, 16(12): 1733-1738.
15. 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.
16. Bartsch T, Brehm M, Zeus T, et al. Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (The TAM-PAD Study). Clin Res Cardiol, 2007, 96(12): 891-899.
17. Sprengers RW, Lips DJ, Moll FL, et al. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg, 2008, 247(3): 411-420.
18. Matoba S, Tatsumi T, Murohara T, et al. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (therapeutic angiogenesis by cell transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J, 2008, 156(5): 1010-1018.
19. Kirana S, Stratmann B, Prante C, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract, 2012, 66(4): 384-393.
20. Dubsky M, Jirkovska A, Bem R, et al. Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment. Diabetes Metab Res Rev, 2013, 29(5): 369-376.
21. Iwase T, Nagaya N, Fujii T, et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res, 2005, 66(3): 543-551.
22. Ishikane S, Ohnishi S, Yamahara K, et al. Allogeneic injection of fetal membrane-derived mesenchymal stem cells induces therapeutic angiogenesis in a rat model of hind limb ischemia. Stem Cells, 2008, 26(10): 2625-2633.
23. Dash NR, Dash SN, Routray P, et al. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res, 2009, 12(5): 359-366.
24. The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Available at: http://www.cochrane.org/.
25. Lu D, Chen B, Liang Z, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract, 2011; 92(1): 26-36.
26. 张忠, 刘文申, 赵秀兰. 自体骨髓干细胞移植治疗糖尿病足溃疡. 实用临床医学, 2007, 8(8): 58-60.
27. 陈兵, 陆德宾, 梁自文, 等. 自体骨髓间充质干细胞体外扩增后移植治疗糖尿病足. 中国组织工程研究与临床康复, 2009, 13(32): 6227-6230.
28. 甘宇, 李铁男, 于黎丽, 等. 自体骨髓干细胞移植配合中药治疗糖尿病足溃疡的疗效及其与血清 VEGF 水平关系的研究. 中国中西医结合皮肤性病学杂志, 2010, 9(4): 206-209.
29. Koch TG, Heerkens T, Thomsen PD, et al. Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol, 2007, 7(1): 1-9.
30. 王晶, 周敏, 孟荔, 等. 两种分离人骨髓单个核细胞方法的比较. 实用医学杂志, 2009, 25(5): 725-726.
31. 郝洪波, 任思坡, 谢晓东. 密度梯度离心法分离骨髓单个核细胞方法的优化. 吉林医学, 2012, 33(35): 7619-7620.
32. 迟作华, 张洹, 陆琰. 人骨髓间充质干细胞分离方法的比较. 中国组织工程研究, 2006, 10(1): 20-22.
33. 蔡金宏, 林春博, 杨渊. 间充质干细胞分离方法的研究与进展. 中国组织工程研究, 2014, 18(45): 7375-7380.
34. 邢文, 庞爱明, 姚剑峰, 等. 直接铺种结合改良组织块培养法可有效分离人骨髓中的间充质干细胞. 中国实验血液学杂志, 2013, 21(2): 451-454.

Chinese Journal of Evidence-Based Medicine

Autologous bone marrow cell transplantation for patients with diabetic foot: a systematic review

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