Bone Marrow Derived Mesenchymal Stem Cells Protect Against Cisplatin Induced Acute Kidney Injury In Rats By Inhibiting Cell Apoptosis

Acute kidney injury (AKI) is a common syndrome with high mortality and morbidity. Recent developments in stem cell research have shown great promise for the treatment of AKI. The goal of this research was to investigate the therapeutic potential and anti-apoptotic mechanisms of bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of AKI induced by cisplatin in vivo and in vitro. In vivo, adult male Sprague-Dawley rats (n=24) were given BM-MSCs intravenously one day after cisplatin injection. Rats were sacrificed four days after cisplatin injection and the effect of BM-MSCs on cisplatin-induced AKI and anti-apoptotic mechanisms involved were investigated. In vitro, NRK-52E cells, a rat renal proximal tubular cell line, were incubated in BM-MSCs derived conditioned medium or complete medium in the presence or absence of cisplatin, followed by cell proliferation and apoptosis assays. Infusion of BM-MSCs preserved renal function, ameliorated renal tubular lesions, reduced apoptosis and accelerated tubular cell regeneration in rats with cisplatin-induced AKI. Infusion of BM-MSCs also inhibited the activation of two mitogen-activated protein kinases, p38and ERK, down-regulated the expression of Bax and cleaved capase-3, and up-regulated the expression of Bcl-2. BM-MSC-conditioned medium improved NRK-52E cell viability and inhibited apoptosis. In conclusion, our results revealed that injection of rats with BM-MSCs protects renal function and structure in cisplatin-induced AKI by inhibiting cell apoptosis in vivo. BM-MSC conditioned medium can protect renal cells from apoptosis induced by cisplatin in vitro. Hence, infusion of BM-MSCs should be considered as a possible therapeutic agent for the treatment of AKI.