Comparing the therapeutic influence of bone marrow Mesenchymal stem cells versus its derived exosomes against diabetic hepatopathy in rats

Abstract

Diabetes mellitus (DM) is a chronic widespread metabolic disorder, involving a high blood glucose level which causes multiple serious complications including liver, kidney, brain and peripheral nerves damage. Due to the undesirable side effects of the anti-diabetic drugs, the current studies directed to use stem cells and exosomes to overcome the limitations of traditional therapy. We aimed to compare the antidiabetic effect of Bone marrow mesenchymal stem cells (BMMSCs) and its derived exosomes against diabetic hepatopathy induced by streptozotocin (STZ) in albino rats. Our study was conducted on 28 male albino rats divided into 4 groups {control negative non diabetic group, control positive diabetic group, exosomes treated group received (5 × 10⁹ particle/rat) through tail vein twice per week for one month} and Stem cell treated group received (10⁷) BMMSCs through tail vein twice per week for one month. Hepatic structure together with blood glucose level, liver function enzymes were assayed in addition to a lipid profile tests, oxidative stress, and gene expression. Both treated groups by exosomes and stem cells expressed significantly low levels of fasting blood glucose, liver function parameters (ALT, AST, ALP), lipid profile tests (cholesterol and triglycerides), lipid peroxidation index (MDA), with substantial reduction in IL-1β expression compared to diabetic group. Significantly downregulating the VEGF and elevation of eNOS genes and GSH which suggest the effective role provided by BMMSCs and its derived exosomes for treatment of diabetic hepatopathy. Although, the results of both groups showed near average outcomes, the exosome treated group significantly enhanced liver function enzymes and triglyceride, cholesterol level compared to stem cells treated group. These findings were reinforced by the histopathological and immunohistochemistry examination. The latter showed slight but non-significant improvements in VEGF, eNOS, and IL-1β expression. These minor differences together with practical advantages of exosomes make it preferable over BMMSCs in treatment of diabetic hepatopathy.