The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1

Abstract

The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague-Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI.