The Effect of Mesenchymal Stem Cells Derived Microvesicles on the Treatment of Experimental CCL4 Induced Liver Fibrosis in Rats

BACKGROUND AND OBJECTIVES: The release of microvesicles (MVs) from mesenchymal stem cells (MSCs) has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. We investigated the effect of administration of MSC-MVs on the therapeutic potential of carbon tetrachloride (CCL(4)) induced liver fibrosis in rats. METHODS: Our work included: isolation and further identification of bone marrow MSC-MVs by transmission electron microscopy (TEM). Liver fibrosis was induced in rats by CCl(4) followed by injection of prepared MSC-MVs in injured rats. The effects of MSC-MVs were evaluated by biochemical analysis of liver functions, RNA gene expression quantitation for collagen-1α, transforming growth factor β (TGF-β), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF) by real time reverse transcription PCR (RT-PCR) techniques. Finally histopathological examination of the liver tissues was assessed for all studied groups. RESULTS: BM-MSC-MVs treated group showed significant increase in serum albumin levels, VEGF quantitative gene expression (p < 0.05), while it showed a significant decrease in serum alanine transaminase (ALT) enzyme levels, quantitative gene expression of TGF-β, collagen-1α, IL-1β compared to CCL(4) fibrotic group (p < 0.05). Additionally, the histopathological assessment of the liver tissues of BM-MSC-MVs treated group showed marked decrease in the collagen deposition & improvement of histopathological picture in comparison with CCL(4) fibrotic group. CONCLUSIONS: Our study demonstrates that BM-MSC-MVs possess anti-fibrotic, anti-inflammatory, and pro-angiogenic properties which can promote the resolution of CCL(4) induced liver fibrosis in rats.