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

Endocrinologists and nephrologists continually seek new therapeutic approaches for diabetic nephropathy (DN). Lately, mesenchymal stem cell (MSC)-derived exosomes (MSC-EXs) have been applied as natural carriers for targeted drug delivery. Thus, we aim to estimate the therapeutic potential of MSCs-EXs loaded with elemental selenium (Se) or its nanoform (NSe) as a promising cell-free therapy for DN. Eighty rats were split into 8 groups; control, EXs, EXs + Se, EXs + NSe, diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe. After 4 weeks, our results indicated that unloaded or loaded EXs with Se or NSe had renal ameliorating effects, as evidenced by significantly decreased serum levels of urea, uric acid, and creatinine compared to untreated diabetics. 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 markedly 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 all diabetic-treated groups was greatly improved. Likely, the EX-loaded NSe treatment protocol highlighted the DN improvement superiority over the other two treatments.