Cyclosporine (CsA) induced nephrotoxicity is an important complications to limit the long term allograft outcome in kidney transplantation. The aim of this study was to investigate whether the immune modulating and tissue repairing effect of human-adipose tissue derived mesenchymal stem cells (hATMSCs) could protect against chronic cyclosporin (CsA)-induced renal injury in an experimental model. CsA (7.5 mg/kg) and hATMSCs (3 * 10⁶/5 mL) were administered alone and together to Sprague Dawley rats for 4 weeks. The effect of hATMSCs on CsA-induced renal injury was evaluated by assessing renal function, interstitial fibrosis, infiltration of inflammatory cells, and apoptotic cell death. Four weeks of CsA treatment produced typical chronic CsA nephropathy. Combined treatment with CsA and hATMSCs did not prevent these effects and showed a trend toward further renal deterioration. To evaluate why hATMSCs aggravated CsA-induced renal injury, we measured oxidative stress, a major mechanism of CsA-induced renal injury. Both urine and serum 8-hydroxydeoxyguanosine (8-OHdG) levels were higher in the CsA + hATMSC group than in the CsA group (P < 0.05). An in vitro study showed similar results. Although the rate of apoptosis did not differ significantly between HK-2 cells cultured in hATMSCs conditioned medium and those cultured in DMEM, addition of CsA resulted in greater apoptosis in HK-2 cells cultured in hATMSCs conditioned medium. Addition of CsA increased the levels of nitric oxide and 8-OHdG in the hATMSCs-conditioned culture medium. The results of our in vivo and in vitro study suggest that treatment with hATMSCs may provide an oxidative stress-associated harmful effect on CsA-induced renal injury.

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