Exosomes from induced and adipose-derived MSCs regulate NRK-52E cells under hyperglycemic conditions

Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), primarily driven by chronic hyperglycemia and characterized by progressive renal damage. The regenerative potential of mesenchymal stem cell (MSC)-derived exosomes (Exos) has been highlighted. However, the therapeutic effects of Exos derived from induced MSCs (iMSC-Exos) and adipose-derived MSC (ADMSC-Exos) on DN-associated cellular processes remain largely unexplored.

Exos were isolated from iMSCs, ADMSCs, and human gingival fibroblasts (HGF). NRK-52E cells were treated with Exos under normal glucose (NG) and high glucose (HG) conditions. Cell viability, apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and the expression of antioxidant-related genes (Nqol, Nrf2, and Ho-1) were evaluated.

Under NG conditions, Exos enhanced NRK-52E cellular viability. However, under HG conditions, all types of Exos exhibited diminished effects at 24 h, and only ADMSC-Exos and HGF-Exos significantly promoted viability at 48 h. Exos did not significantly alter ROS levels but affected mitochondrial function and the expression of antioxidant-related genes. Specifically, while both ADMSC- and iMSC-Exos enhanced MMP under NG conditions, ADMSC-Exos reduced MMP under HG conditions, and iMSC-Exos consistently enhanced it. Under NG conditions, both iMSC- and ADMSC-Exos upregulated HO-1, whereas under HG conditions, ADMSC-Exos downregulated HO-1 and Nqol.

The findings highlighted the distinct roles of iMSC-Exos and ADMSC-Exos, with both showing limited efficacy under HG. However, iMSC-Exos enhanced mitochondrial function under HG, suggesting a potential therapeutic benefit that requires further investigation.