1.The Effect of Mesenchymal Stem Cells Derived Microvesicles on the Treatment of Experimental CCL4 Induced Liver Fibrosis in Rats
Dina SABRY ; Abbas MOHAMED ; Manar MONIR ; Heba A IBRAHIM
International Journal of Stem Cells 2019;12(3):400-409
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 (CCL₄) 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 CCl4 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 CCL₄ 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 CCL₄ 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 CCL₄ induced liver fibrosis in rats.
Alanine Transaminase
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Animals
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Bone Marrow
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Carbon Tetrachloride
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Collagen
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Gene Expression
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Liver Cirrhosis
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Liver
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Mesenchymal Stromal Cells
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Microscopy, Electron, Transmission
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Polymerase Chain Reaction
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Rats
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Reverse Transcription
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RNA
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Serum Albumin
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Transforming Growth Factors
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Vascular Endothelial Growth Factor A