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.

Thioacetamide (TAA)-induced liver fibrosis, triggered by inflammation and oxidative stress, is prompted by hepatic stellate cells (HSCs) activation via several pathways. This study explores the hepatoprotective effect of aloe vera gel (AVG) extract and bone marrow mesenchymal stem cells (BM-MSCs) transplantation on regulating long intergenic noncoding RNA (lincRNA-p21) and microRNA (miR-17-5p) expressions and their impact on TGF-β1/Smad-3 and Wnt-10a/ β-Catenin cascades in TAA-induced liver damage. The study involved 48 adult male albino rats divided into four groups:control, TAA, TAA treated with BM-MSCs, and TAA treated with BM-MSCs+AVG extract. After 8 weeks, liver enzymes and hepatic oxidative parameters were evaluated alongside lincRNA-p21, miR-17-5p, TGF-β1, Smad-3, Wnt-10a, and β-Catenin expressions. Liver tissue sections were examined by light and electron microscopes and analyzed morphometrically. Group II showed increased aspartate aminotransferase, alanine aminotransferase, malondialdehyde, reduced glutathione levels, and deteriorated hepatocytes with distorted mitochondria and dilated rough endoplasmic reticulum. Group IV restored lincRNA-p21 expression, which downregulated miR-17-5p and suppressed activated HSCs by inhibiting TGF-β1/Smad-3 and Wnt-10a/β-Catenin pathways, and improved hepatic tissue architecture. Additionally, immunohistochemically, alpha-smooth muscle actin and cyclin D1 expressions were markedly decreased in group IV compared to group II. We concluded that AVG suppresses fibrotic pathways, boosts BM-MSCs differentiation, and reduces HSCs activation in liver fibrosis caused by TAA.