Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes

Purpose: The purpose of this study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) on podocytes of puromycin amino nuclear glucoside (PAN) -induced nephrosis in mice. Methods: Mice were randomly divided into Control, PAN and BMSC groups. Mice were injected with PAN (0.5 mg/g weight) via the tail vein. The 24 h urinary protein was obtained after modelling, and urinary protein excretion was determined. The blood and kidney specimens were isolated after the tenth day of modelling. Blood samples were collected for measuring serum creatinine (SCr) and blood urea nitrogen (BUN). A sample of kidney was taken for observing pathological changes through hematoxylin-eosin staining and electron microscopy, and the rest of the kidney was used for detecting the protein and mRNA expression of nephrin, CD2AP, synaptopodin, TRPC6 by real-time quantitative PCR, Western-blot and immunohistochemistry. Results: After PAN injection, podocyte foot process fusion was detected by electron microscopy, and the 24 h urinary protein excretion increased compared with control mice on days 3, 7 and 10 post-PAN injection (P<0.05). Serum albumin decreased compared with control mice after day 10 (P<0.05). The phenomenon of foot process fusion was ameliorated after administration of BMSC, and 24 h urinary protein decreased (P<0.05), while serum albumin increased (P<0.05). Nephrin, CD2AP and synaptopodin in the glomerular slit diaphragm were up-regulated compared to PAN nephropathy model mice (P<0.05) while TRPC6 was down-regulated (P<0.05). Conclusions: Administration of BMSC reduced foot process fusion and urine protein excretion, and protected against podocyte damage caused by PAN.