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 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 that unloaded or loaded EXs with Se or NSe had renal ameliorating effects, as evidenced by significantly (p ˂ 0.05) decreased serum levels of urea by 32.25, 41.29, and 51.61% (from 31 mg/dl ± 0.74 in the diabetic group to 21 ± 0.22, 18.2 ± 0.26, and 15 ± 0.28 respectively), uric acid by 40.42, 46.80, and 59.57% (from 4.7 mg/dl ± 0.43 in the diabetic group to 2.8 ± 0.03, 2.5 ± 0.22, and 1.9 ± 0.24 respectively), and creatinine by 44.49, 53.05, and 60.14% (from 4.09 mg/dl ± 0.17 in the diabetic group to 2.27 ± 0.12, 1.92 ± 0.18, and 1.63 ± 0.16 respectively) 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 (by 26.32, 35.63, and 45.46% respectively), NO (by 31.46, 38.89, and 46.71% respectively), H₂O₂ (by 28.36, 41.43, and 50.25% respectively) levels coupled with increased GSH (by 60.05, 74.57, and 111.75% respectively), SOD (by 54.01, 73.52, and 97.32% respectively), CAT (by 35.47, 65.45, and 96.36% respectively), and GPX (by 56.95, 87.30, and 136.51% respectively), besides their anti-inflammatory and antiapoptotic effects, indicated by the decreased renal levels of IL-6 (by 36.32, 45.69, and 55.06% respectively), TGF-β (by 37.85, 45.39, and 55.28% respectively), TNF-α (by 41.33, 48.55, and 62.09% respectively), BAX (by 28.60, 40, and 53% respectively), caspase-3 (by 31.13, 42.45, and 64.15% respectively), and P53 (by 24.50, 50.39, and 61.76%) respectively, with Bcl-2 upregulation (by 86.85, 100.57, and 138. 28% respectively). Consequently, the kidney architecture in the three diabetic-treated groups was greatly improved. Likely, the EX-loaded NSe treatment protocol highlighted the DN improvement superiority over the other two treatments.