Evaluation of mesenchymal stem cells-derived exosomes and conditioned medium as a potential treatment for induced type 1 diabetes mellitus in adult male albino rats

Diabetes mellitus (DM) is a metabolic condition marked by disrupted insulin regulation. Mesenchymal stem cellderived exosomes and conditioned medium (CM) have emerged as promising therapeutic candidates for DM. This research explored the medical benefits of exosomes and CM in treating streptozotocin-induced type 1 DM (T1DM) in rats, comparing their efficacy to bone marrow-derived mesenchymal stem cells (BM-MSCs). Fifty albino rats were grouped into five groups (n=10 each): healthy controls, untreated T1DM rats, T1DM rats treated with intravenous BM-MSCs, T1DM rats treated with intravenous exosomes, and T1DM rats treated with intravenous CM. Plasma glucose and insulin concentrations were monitored weekly. Pancreatic β-cell regeneration was analyzed via qRT-PCR, focusing on the expression levels of TGF-β, Smad3, Ngn3, Pdx1, MafA, and insulin genes. Histological evaluation of pancreatic tissue regeneration was performed at weeks 2 and 4 using hematoxylin & eosin and Masson's trichrome stains. The exosomes- and CM-treated groups demonstrated significantly higher expression of β-cell regeneration markers (TGF-β, Smad3, Ngn3, Pdx1, MafA, and insulin) than the BM-MSCs group. Additionally, these groups demonstrated a marked rise in the area percentage of pancreatic islets and a significant reduction in pancreatic fibrosis, with more pronounced effects at week 4. Exosomes and CM exhibit superior therapeutic efficiency and regenerative potential over BM-MSCs in T1DM, suggesting their promise as cell-free alternatives for diabetes treatment.