Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Biol Blood Marrow Transplant. 2013 Apr;19(4):538-46. doi: 10.1016/j.bbmt.2013.01.001. Epub 2013 Jan 4.
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 × 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.
间充质干细胞（MSC）可减轻糖尿病小鼠的蛋白尿并维持其正常的肾脏组织学结构。然而，MSC 对肾小球足细胞损伤的影响仍不确定。本研究旨在评估 MSC 对链脲佐菌素（STZ）诱导的糖尿病大鼠足细胞损伤的影响。STZ（65mg/kg，腹腔内）注射诱导糖尿病 30 天后，将糖尿病大鼠的肾动脉内分别给予 MSC 培养基或 2×10(6)个增强型绿色荧光蛋白标记的 MSC。通过免疫荧光分析来追踪 MSC 的体内迁移。在 MSC 输注后第 60 天测量与糖尿病相关的生理和生化参数。还评估了足细胞标志物（nephrin 和 podocin）、足细胞存活因子（VEGF 和 BMP-7）的表达以及足细胞的超微结构病理学。仅在接受 MSC 输注的左肾肾小球中检测到 MSC。与 MSC 培养基处理的糖尿病大鼠相比，MSC 治疗组的肾脏重量、肾脏体重比、肌酐清除率和尿白蛋白与肌酐比值均有所降低，但治疗对血糖或体重水平没有影响。此外，MSC 治疗减少了足细胞的丢失、足突的融合、足突的增宽、肾小球基底膜（GBM）的增厚以及肾小球 nephrin 和 podocin 的丢失。最重要的是，MSC 处理的肾脏表达了更高水平的 BMP-7，但 VEGF 水平没有增加。我们的研究结果清楚地表明，经动脉内给予 MSC 可预防白蛋白尿的发生以及足细胞的任何损伤或丢失，尽管血糖水平没有改善。MSC 的保护作用可能部分通过增加 BMP-7 的分泌来介导。
