Effect of Exosomes Derived from Mesenchymal Stem Cell on Hepatic Regeneration in Carbon Tetrachloride Induced Acute Liver Injury in Adult Male Albino Rats. Histological Study

Abstract

Abstract Background Acute liver failure (ALF) is one of the emergency conditions. Carbon tetrachloride (CCl4) has been widely used to induce experimental hepatic damage. Bone marrow mesenchymal stem cell derived (BM-MSC) exosomes are broadly applied to regenerative approaches for various disorders serving the therapeutic effects of MSCs. Aim of the Work The study analyzed microscopically and biochemically, the regenerative power of the BM-MSC exosomes on the experimentally induced acute hepatic injury. Materials and Methods Fifty-five male adult Wistar albino rats were randomly divided into three groups: Group (I) control group, group II [given a single intraperitoneal injection of carbon tetrachloride (CCl4) (3% vol/vol in olive oil) at 0.05 ml/kg body weight] and group III [given a single tail vein injection of 50 μg of BM-MSC exosomes in 100 μl phosphate buffered saline 24 hours post-CCl4]. The rats were sacrificed after seven days. Biochemical analysis of AST and ALT was performed. Histological examination of liver tissue was performed through light microscopy of hematoxylin and eosin and Masson trichrome stained sections. Transmission electron microscopy (TEM) of liver tissue was carried out. Morphometric and statistical studies were done. Results By light microscopy, H&E-stained sections of Group II (CCl4 treated) revealed altered hepatic architecture with focal cellular infiltration. Congestion and dilatation of portal veins with periportal cellular infiltration were detected. Widening and endothelial discontinuity of the central veins and disorganization and obliteration of some blood sinusoids were demonstrated. Most hepatocytes appeared with darkly acidophilic cytoplasm and condensed nuclei, while others appeared with pyknotic nuclei with vacuolated cytoplasm. In Masson trichrome stained sections, there was a significant increase in the collagen fibers around the central veins and portal triads, and between hepatic cords. TEM examination, hepatocytes displayed irregular heterochromatic nuclei and rarified cytoplasm with plenty of lipid droplets. Hepatic stellate cells were devoid of lipid droplets. The epithelial cell lining the bile ductules had few short microvilli Inflammatory cells were seen near the ductular basal border. Biochemically, there was a significant increase in both ALT & AST levels in group II. The exosomes treated group (III) revealed marked amelioration of the previously mentioned histopathological and biochemical changes compared to the control group. Conclusion The acute CCl4 induced injury was significantly attenuated by BM-MSC exosomes therapy, and is characterized by an increase in hepatocyte proliferation, significant regression of collagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and biochemically.