CCN2 and Hepatic fibrosis: Additionally, during liver injury, hepatic stellate cells (HSCs) and EVs produced by MSC interact resulting in the release of connective tissue growth factor (CCN2),90 which by binding integrin v3 or v5 with heparan sulfate proteoglycan ligands, can signal to endothelial cells to modulate activation.91 On the other hand, MSC-EVs affect target cells via activating the transcription factors Twist-1, miR-214, and miR-199a-5p.89 Despite numerous preclinical studies on liver fibrosis with MSC-EVs, it remains unclear whether MSCs-EV stimulate local damage liver cells.