Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury

Mesenchymal Stem Cells (MSCs) derived Extracellular Vesicles (EVs) have emerged as an effective candidate for amelioration of liver fibrosis. However, the effect and the mechanisms of MSC-EVs in liver repair remains elusive. In this study, we have evaluated the differential regenerative efficacy of EVs derived from two different human tissue-specific MSCs (Adipose tissue; AD-MSC and Wharton’s Jelly; WJ-MSC), in a murine model of chronic liver fibrosis. Mouse model of chronic liver injury was induced by carbon tetrachloride (CCl₄) injection, followed by administration of EVs via the tail vein. Both quantitative and qualitative assessment was done to evaluate the hepatic regenerative potential of tissue specific MSC-extracellular vesicles. EVs, regardless of their MSC source, were found to be effective in alleviating chronic liver fibrosis, as demonstrated by macroscopic alterations in the liver. According to the findings of the comprehensive study, there were subtle variations in the tissue specific MSCs-EVs mediated approaches. A greater anti-fibrotic impact was demonstrated by AD-MSC derived EVs through extracellular matrix alteration and hepatocyte proliferation. WJ-MSC EVs, on the other hand, have an anti-inflammatory effect, as evidenced by alterations in the expression of pro- and anti-inflammatory cytokines. Furthermore, cargo profiling of these EVs revealed differences in the miRNA and protein expression, as well as the pathways that they were associated.

Graphical abstract