title: Human adipose-derived mesenchymal stem cells repair cisplatin-induced acute kidney injury through antiapoptotic pathways.
abstract: Cisplatin has been hypothesized to induce nephrotoxicity through triggering the apoptosis of tubular cells; however, the drug remains widely administered for the treatment of tumors. Recently, mesenchymal stem cells (MSCs) have been demonstrated to protect the kidney from the adverse effects induced by cisplatin. The aim of the present study was to investigate the mechanisms underlying the protective effects of human adipose-derived MSCs (AD-MSCs) on kidney function and tubular cells. Sprague-Dawley rats were divided into three groups, which included the healthy controls, those subjected to cisplatin-induced acute kidney injury (AKI) for 24 h without subsequent treatment and those subjected to cisplatin-induced AKI for 24 h, followed by AD-MSC engraftment. The rats were sacrificed at day 5 and the effects were analyzed using various methods, including biochemical analysis, structural examination and cell tracking experiments. In addition, anin vitroexperiment with NRK-52E cells was performed. The cells were divided into three groups, including the healthy control, cisplatin induction and cisplatin induction with co-culture of AD-MSCs, and were subsequently assessed with a Transwell assay. After culture for four days, the cells were lysed and the total protein extract was subjected to western blot analysis. Cisplatin-induced renal dysfunction and tissue damage was shown to recover following AD-MSC infusion, although there were few AD-MSCs observed around the injured kidney tubules in the kidney. When the cisplatin-treated NRK-52E cells were co-cultured with AD-MSCs, the activation of p38 and BAX were inhibited, while the expression of Bcl-2 was upregulated, as compared with the cisplatin-treated NRK-52E cells that were not co-cultured. Therefore, AD-MSCs were shown to markedly improve cisplatin-induced renal failure and tubular cells necrosis through the secretion of certain factors, which subsequently inhibited the apoptosis pathwayin vitro. It was hypothesized that AD-MSC secretion was triggered by the injured tubular cells. Thus, AD-MSCs may be important for the therapy of patients with renal injury due to their antiapoptotic capacity.
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Oncology, Ren Ming Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Qinyong
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Molecular Chemistry, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Dongcheng
authors.initials: D
authors.lastname: Wu
keywords: acute kidney injury; adipose derived-mesenchymal stem cells; antiapoptosis