Mesenchymal stem cell transplantation for post-transplant renal function: a Meta-analysis

doi:10.3969/j.issn.2095-4344.2016.36.017

Abstract

Abstract:

BACKGROUND: In recent years, with the use of new immunosuppressive agents, the survival rate of renal graft is greatly improved, but accompanied by lots of side effects and unchanged long-term graft survival. Mesenchymal stem cells (MSCs) have aroused people’s great interest, while their efficacy in kidney transplantation remains controversial.
OBJECTIVE: To evaluate the efficacy of MSCs transplantation on post-transplant renal graft function with a systematic review.
METHODS: PubMed, EMBASE, the Cochrane Library database, the Cochrane Central Register of Controlled Trials, Wanfang database and China National Knowledge Infrastructure (CNKI) were searched until November 2015. Revman 5.3 was used for statistical analysis.
RESULTS AND CONCLUSION: A total of 6 randomized controlled trials were included, including 1 166 patients. Meta-analysis results showed that at 1, 2 weeks and 1 month after kidney transplantation, the posttransplantation estimated glomerular filtration rates in the MSC-treated group were significantly higher than those in the control group (P < 0.05). At 1, 3, 6, 12 months after kidney transplantation, the posttransplantation serum creatinine levels showed no significant difference between the MSC-treated group and the control group (P > 0.05). To conclude, MSC-based immunosuppression regimen is superior to current standard immunotherapy in improving renal graft function in the early stage after kidney transplantation, but the clinical efficacy is diminished in the later period. Therefore, further investigation using large-scale randomized controlled trials is warranted.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mesenchymal Stem Cells, Kidney Transplantation, Glomerular Filtration Rate, Creatinine, Meta-Analysis, Tissue Engineering

CLC Number:

R394.2

Chen Cheng, Gu Yu-wei, Zhang Jun, Hu Lin-kun, Wei Xue-dong, Hou Jian-quan. Mesenchymal stem cell transplantation for post-transplant renal function: a Meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(36): 5432-5439.

Figures/Tables 4

2.3 Meta分析结果 2.3.1 血清肌酐水平评价移植肾指标见图2。有3个研究报道了移植后1个月的血清肌酐水平[8-10]，共58例，实验组和对照组均为29例。异质性检验显示各研究之间有异质性(P=0.02，I2=73%)，故采用随机效应模型进行Meta分析。结果显示间充质干细胞治疗组与对照组相比，其差异无显著性意义[WMD=3.68，95%CI (-9.09，16.45)，P=0.57]。有3个研究报道了移植后3个月的血清肌酐水平[8-10]，共58例，实验组和对照组均为29例。异质性检验显示各研究之间有异质性(P=0.01，I2=76%)，故采用随机效应模型分析。结果显示间充质干细胞治疗组与对照组相比，其差异无显著性意义[WMD=1.09，95%CI(-13.96，16.14)，P=0.89]。有3个研究报道了移植后6个月的血清肌酐水平[8-10]，共58例，实验组和对照组均为29例。异质性检验显示各研究之间有异质性(P=0.005，I2=81%)，采用随机效应模型分析。Meta分析结果显示间充质干细胞治疗组与对照组相比，其差异无显著性意义[WMD=3.39，95%CI (-8.64，15.41)，P=0.58]。有3个研究报道了移植后12个月的血清肌酐水平[8-11]，共954例，其中实验组625例，对照组329例。异质性检验显示各研究之间有异质性(P=0.002，I2=80%)，故采用随机效应模型分析。Meta分析结果显示间充质干细胞治疗组与对照组相比，其差异无显著性意义[WMD=1.05，95%CI(-5.97，8.07)，P=0.77]。 2.3.2 肾小球滤过率估计值评价移植肾指标见图3。有2个研究报道了移植后1周的肾小球滤过率估计值水平[12-13]，共295例，其中实验组148例，对照组147例。异质性检验显示各研究之间无异质性(P=0.68，I2=0%)，故采用固定效应模型分析，结果显示间充质干细胞治疗组的肾小球滤过率估计值比对照组平均高23.28 mL/min per 1.73 m2，其差异有显著性意义[WMD=23.28，95%CI(20.97，25.60)，P < 0.000 01]。有2个研究报道了移植后2周的肾小球滤过率估计值水平[12-13]，共295例，其中实验组148例，对照组147例。异质性检验显示各研究之间有异质性(P=0.02，I2=76%)，采用随机效应模型分析，Meta分析结果示间充质干细胞治疗组的肾小球滤过率估计值比对照组平均高12 mL/min per 1.73 m2，其差异有显著性意义[WMD=12.00，95%CI(6.11，17.89)，P < 0.000 1]。有2个研究报道了移植后4周的肾小球滤过率估计值水平[12-13]，共295例。其中实验组148例，对照组147例。异质性检验显示各研究之间有异质性(P < 0.000 1， I，故采用固定效应模型分析，结果示间充质干细胞治疗组的肾小球滤过率估计值比对照组平均高8.74 mL/min per 1.73 m2，其差异有显著性意义[WMD=8.74，95%CI(0.58, 16.89)，P=0.04]。2=89%)"

References

[1] Hardinger KL, Koch MJ, Brennan DC. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy. 2004;24(9):1159- 1176.
[2] Therasse A, Wallia A, Molitch ME. Management of post-transplant diabetes. Curr Diab Rep. 2013; 13(1): 121-129.
[3] Guerra G, Ilahe A, Ciancio G. Diabetes and kidney transplantation: past, present, and future. Curr Diab Rep. 2012;12(5):597-603.
[4] Ren G, Chen X, Dong F, et al. Concise review: mesenchymal stem cells and translational medicine: emerging issues. Stem Cells Transl Med. 2012;1(1): 51-58.
[5] Algeri M, Conforti A, Pitisci A, et al. Mesenchymal stromal cells and chronic inflammatory bowel disease. Immunol Lett. 2015;168(2):191-200.
[6] Le Blanc K, Ringdén O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262(5):509-525.
[7] Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559.
[8] Peng Y, Ke M, Xu L, et al. Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study. Transplantation. 2013;95(1):161-168.
[9] 朱景辉.自体BM-MSC诱导亲属活体供肾移植免疫耐受的临床研究[D]. 广州:广州医学院, 2013.
[10] 陈正. BM-MSC诱导移植免疫耐受和修复慢性移植肾损伤的初步研究[D].长沙:中南大学,2013.
[11] Vanikar AV, Trivedi HL. Stem cell transplantation in living donor renal transplantation for minimization of immunosuppression. Transplantation. 2012;94(8): 845-850.
[12] Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA. 2012;307(11):1169-1177.
[13] 吴卫真,谭建明,孙星慧,等. 术前自体间充质干细胞输注用于肾移植诱导治疗的临床研究[J]. 中华器官移植杂志, 2011,32(11): 647-650.
[14] Hariharan S, McBride MA, Cherikh WS, et al. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int. 2002; 62(1):311-318.
[15] Bank JR, Rabelink TJ, de Fijter JW, et al. Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients. J Immunol Res. 2015;2015:391797.
[16] Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol. 2006; 17(10):2937-2944.
[17] Chen C, Hou J. Mesenchymal stem cell-based therapy in kidney transplantation. Stem Cell Res Ther. 2016;7: 16.
[18] Liu H, Xia X, Li B. Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues. Exp Biol Med (Maywood). 2015; 240(8):1099-1106.
[19] Wang S, Qu X, Zhao RC.Clinical applications of mesenchymal stem cells.J Hematol Oncol. 2012;5:19.
[20] Schrepfer S, Deuse T, Reichenspurner H, et al. Stem cell transplantation: the lung barrier. Transplant Proc. 2007;39(2):573-576.
[21] Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev. 2009;18(5):683-692.
[22] Leuning DG, Reinders ME, de Fijter JW, et al. Clinical translation of multipotent mesenchymal stromal cells in transplantation. Semin Nephrol. 2014;34(4):351-364.
[23] Crop MJ, Korevaar SS, de Kuiper R, et al. Human mesenchymal stem cells are susceptible to lysis by CD8(+) T cells and NK cells. Cell Transplant. 2011; 20(10):1547-1559.
[24] Roemeling-van Rhijn M, Weimar W, Hoogduijn MJ. Mesenchymal stem cells: application for solid-organ transplantation. Curr Opin Organ Transplant. 2012; 17(1):55-62.
[25] Zhang W, Qin C, Zhou ZM. Mesenchymal stem cells modulate immune responses combined with cyclosporine in a rat renal transplantation model. Transplant Proc. 2007;39(10):3404-3408.
[26] Inoue S, Popp FC, Koehl GE, et al. Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation. 2006;81(11): 1589-1595.
[27] 张磊,陈正,谢斯盛,等.自身间充质干细胞治疗慢性移植物肾病的安全性与可行性[J].中国组织工程研究,2014, 18(32):5140-5145.
[28] El-Ansary M, Saadi G, Abd El-Hamid SM. Mesenchymal stem cells are a rescue approach for recovery of deteriorating kidney function. Nephrology (Carlton). 2012;17(7):650-657.