Therapeutic potential of mesenchymal stem cells-derived exosomes loaded with elemental or nano selenium on diabetic nephropathy

Abstract Endocrinologists and nephrologists continually seek new therapeutic approaches for diabetic nephropathy (DN). Lately, mesenchymal stem cells (MSCs)-derived exosomes (MSCs-EXs) have been applied as natural carriers for targeted drug delivery. Thus, we aim to estimate the therapeutic potentialities of MSCs-EXs loaded with ordinary selenium (Se) or its nanoform (NSe) as a promising cell-free therapy in diabetic nephropathy (DN). Eighty rats were randomly split into 8 groups; control, EXs, EXs + Se, EXs + NSe, diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. After 4 weeks, our results indicated renal hypolipidemic and renal ameliorating effects of unloaded or loaded EXs with Se or NSe, evidenced by the declined serum levels of urea, uric acid, and creatinine, compared to diabetic-untreated rats. Such observations might be a reflection of the observed antioxidant activity of both EXs alone or in the combined form with either Se or NSe, evidenced by decreased renal MDA, NO, H₂O₂ levels coupled with increased GSH, SOD, CAT, and GPX, besides their anti-inflammatory and antiapoptotic effects, indicated by the decreased renal levels of IL-6, TGF-β, TNF-α, BAX, caspase-3, and P53, with Bcl-2 upregulation. Consequently, the kidney architecture in the three diabetic-treated groups was greatly improved. Likely, the EXs-loaded NSe treatment protocol highlighted the DN improvement superiority most significantly compared to the other protocols.