Human Adipose Tissue Derived Mesenchymal Stem Cells Aggravate Chronic Cyclosporin Nephrotoxicity by the Induction of Oxidative Stress

Abstract

The aim of this study was to investigate whether hATMSCs protect against cyclosporine (CsA)-induced renal injury. CsA (7.5 mg/kg) and hATMSCs (3×106/5 mL) were administered alone and together to 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+hATMSCs 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 oxidative stress in the hATMSCs-conditioned medium. The results of our study suggest that treatment with hATMSCs may aggravate CsA-induced renal injury because hATMSCs cause oxidative stress in the presence of CsA.