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 cell-derived 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.