Mesenchymal Stem Cells Ameliorate Podocyte Injury and Proteinuria in a Type 1 Diabetic Nephropathy Rat Model

被引:120
作者
Wang, Shuai [1 ,2 ,3 ]
Li, Yi [1 ,2 ]
Zhao, Jinghong [1 ,2 ]
Zhang, Jingbo [1 ,2 ]
Huang, Yunjian [1 ,2 ]
机构
[1] Third Mil Med Univ, Xinqiao Hosp, Inst Nephrol Chongqing, Chongqing 400037, Peoples R China
[2] Third Mil Med Univ, Xinqiao Hosp, Dept Nephrol, Chongqing 400037, Peoples R China
[3] Chengdu Mil Gen Hosp, Dept Nephrol, Chengdu, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
Mesenchymal stem cells; Cell therapy; Diabetic nephropathy; Podocyte injury; Proteinuria; Bone morphogenetic protein-7; RENAL-FAILURE; STROMAL CELLS; SLIT DIAPHRAGM; KIDNEY; DIFFERENTIATION; TRANSPLANTATION; ALLOXAN; REPAIR; REGENERATION; MECHANISMS;
D O I
10.1016/j.bbmt.2013.01.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mesenchymal stem cells (MSC) attenuate albuminuria and preserve normal renal histology in diabetic mice. However, the effects of MSC on glomerular podocyte injury remain uncertain. The aim of this study was to evaluate the effects of MSC on podocyte injury in streptozotocin (STZ)-induced diabetic rats. Thirty days after diabetes induction by STZ injection (65 mg/kg, intraperitoneally) in Sprague-Dawley rats, the diabetic rats received medium or 2 x 10(6) enhanced green fluorescent protein-labeled MSC via the renal artery. In vivo tracking of MSC was followed by immunofluorescence analysis. Diabetes-related physical and biochemical parameters were measured on day 60 after the MSC infusion. The expression of podocyte markers (nephrin and podocin), podocyte survival factors (VEGF and BMP-7), and the ultrastructural pathology of podocytes were also assessed. MSC were only detected in the glomeruli from the left kidney receiving MSC infusion. Compared with medium-treated diabetic rats, rats treated with MSC showed a suppressed increase in kidney weight, kidney to body weight index, creatinine clearance rate, and urinary albumin to creatinine ratio; however, the treatment had no effect on blood glucose or body weight levels. Furthermore, the MSC treatment reduced the loss of podocytes, effacement of foot processes, widening of foot processes, thickening-of glomerular basal membrane (GBM), and loss of glomerular nephrin and podocin. Most important, MSC-injected kidneys expressed higher levels of BMP-7 but not of VEGF. Our results clearly demonstrated that intra-arterial administration of MSC prevented the development of albuminuria as well as any damage to or loss of podocytes, though there was no improvement in blood sugar levels. The protective effects of MSC may be mediated in part by increasing BMP-7 secretion. (C) 2013 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:538 / 546
页数:9
相关论文
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