Impact of preconditioning stem cells with all-trans retinoic acid signaling pathway on cisplatin-induced nephrotoxicity by down-regulation of TGFβ1, IL-6, and caspase-3 and up-regulation of HIF1α and VEGF.

The survival reduction after transplantation limited the clinical uses of stem cells so the current study explored preconditioning adipose-derived stem cells (ADMSCs) and all-trans retinoic acid (ATRA) effects on cisplatin that caused acute kidney injury (AKI). One hundred and fifty Sprague-Dawley male rats were distributed into five groups: control group; Cisplatin (CIS) group; CIS and ATRA group; CIS and ADMSC group, and CIS, ATRA, and ADMSCs group. Ten rats were euthanized after 3rd, 7th, and 11th days from CIS injection. Renal function, molecular studies, and histopathological analysis were studied. The preconditioning of ADMSCs with ATRA increased the viability of the cells which was reflected in the amelioration of kidney functions after CIS injection by the significant reduction of serum creatinine, microalbuminuria, as well as NO, and the significant rise of creatinine clearance, as well as SOD compared to the group of cisplatin. ATRA also supported ADMSCs by a significant down-regulation of caspase-3, il-6 and TGFβ1, and a significant up-regulation of HIF1, VEGF and CD31 compared to group of cisplatin which reversed the cisplatin effect. ATRA increased renoprotective properties of ADMSCs against cisplatin- induced AKI by reducing the apoptosis, inflammation, and stimulating angiogenesis.