Investigation Of Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Ischemia/reperfusion Acute Renal Failure

Objective To obtain sufficient human umbilical cord mesenchymal stem cells(ucMSCs) used in transplantation in vitro and identify their characteristics.To establish an animal model of acute renal failure(ARF) induced by ischemia and reperfusion(I/R) and evaluate the curative effect on renal injury repair after ucMSC transplantation,further to investigate the mechanism.Methods ucMSCs were isolated by adherent culture method. Comparing with bone marrow MSCs,their basical characteristics such as morphology,ultramicrostructure,surface antigens and gene expression were analysed.The renal function was also studied by using condition culture method.Renal I/R injury model was established by clamping bilateral pedicles for 60 minutes and reperfusion.1.0×10~6 ucMSCs were administrated to rats at 16 hours after injury by left carotid artery. Creatinine(Cr) and urea nitrogen(BUN) in serum were detected at different time points.Histopathological analyses were performed. Real-time PCR was used to quantify gene expression.The location of ucMSC and calculation of tubular regeneration were detected by immunohistochemistry.Results The characteristics of ucMSC were similar to bone marrow MSC in vitro.After cytokine induction,hypoxia/reoxygenation and coculture,ucMSCs were induced to form renal like cells and increase the expression of renoprotective cytokines.The levels of Cr and BUN were significantly decreased after ucMSC transplantation in vivo.The renal structures were also improved with less hyperemia and inflammatory cells.The results for PCR and immunohistochemistry showed that ucMSCs located in injured renal tissues.In addition,the expression of proliferative nuclear cell antigen(PCNA) in ucMSC treated groups was more than control groups.The data for Real-time PCR showed that the expression of caspase-3 and IL-1βin renal tissues was markedly decreased in ucMSC treated rats.The ucMSC transdifferentiating into renal like cell was not observed.Conclusions Human ucMSCs ameliorate ischemia and reperfusion induced acute renal failure in rats through paracrine actions,further demonstrating that ucMSC therapy has promise as a novel intervention in ARF.