Anti-fibrosis Effects of Extracellular Vesicles Generated From Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells in Chronic Liver Injury

Background and Aim: Mesenchymal stromal cells (MSCs) exert theirhepato-protective effects more probably through the secretion offunctional extracellular vesicles (EVs) in liver injuries. Human embryonicstem cell-derived MSCs (ES-MSCs) are increasingly applied both in vitroand in vivo due to the high proliferation rate and immunomodulatorypotential. The aim of this study is to investigate the therapeutic potentialof ES-MSC derived EVs (ES-MSC EVs) in thioacetamide-induced chronicliver injury (CLI).Methods: Inhibitory effects of ES-MSC EVs were determined onperipheral blood mononuclear cells (PBMCs) proliferation using mixedlymphocyte reaction (MLR) assay in vitro. To induce CLI model, 200 mg/kg TAA toxin were injected twice weekly for 16 weeks. After cirrhosisinduction, ES-MSC EVs were injected intrasplenically under the guidanceof ultrasound.Results: Human ES-MSCs EVs could elicit potent immunosuppressionpotential compared to human bone marrow (BM)-MSCs and humanadipose (AD)-MSCs in vitro. Moreover, ES-MSC EVs demonstratedimmunosuppression in TAA-induced CLI. ES-MSC EVs are involved inreduction of fibrosis, collagen density and portal vein diameter as well.Downregulation of fibrosis-related genes (Col1α, αSMA, and TIMP1) andupregulation in collagenases (MMP9 and MMP13) and anti-inflammatorycytokine (IL-10) were detected following administration of ES-MSC EVsin CLI rat model.Conclusion: The results of this study provided a new approach that ESMSCEVs could be considered as allogenic cell-free products in liverdiseases.

کلیدواژه ها:

Mesenchymal Stromal Cells ، Extracellular vesicles ، Chronic liver injury