Bone marrow-derived mesenchymal stem cells protect against cisplatin-induced acute kidney injury in rats by inhibiting cell apoptosis

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Abstract
Acute kidney injury (AKI) is a common syndrome with a high mortality and morbidity rate. Recent developments in stem cell research have shown great promise for the treatment of AKI. The aim of this study was to investigate the therapeutic potential and anti-apoptotic mechanisms of action of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the treatment of AKI induced by cisplatin in vivo and in vitro. In vivo, adult male Sprague-Dawley rats (n=24) were administered BM-MSCs intravenously one day after cisplatin injection. The rats were sacrificed four days after the cisplatin injection and the effects of BM-MSCs on cisplatin-induced AKI, as well as the anti-apoptotic mechanisms involved were investigated. In vitro, NRK-52E cells, a rat renal proximal tubular cell line, were incubated in conditioned medium or complete medium in the presence or absence of cisplatin, followed by cell proliferation and apoptosis assays. The infusion of BM-MSCs preserved renal function, ameliorated renal tubular lesions, reduced apoptosis and accelerated tubular cell regeneration in the rats with cisplatin-induced AKI. The infusion of BM-MSCs also inhibited the activation of two mitogen-activated protein kinases, p38 and ERK, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. BM-MSC-conditioned medium improved NRK-52E cell viability and inhibited apoptosis. In conclusion, our results demonstrate that injecting rats with BM-MSCs protects renal function and structure in cisplatin-induced AKI by inhibiting cell apoptosis in vivo. BM-MSC-conditioned medium protects renal cells from apoptosis induced by cisplatin in vitro. Hence, the infusion of BM-MSCs should be considered as a possible therapeutic strategy for the treatment of AKI.

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