title: Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis.
abstract: Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the therapy of diseases. Exosomes excreted from MSCs can reduce myocardial ischemia/reperfusion damage and protect against acute tubular injury. However, whether MSC-derived exosomes can relieve liver fibrosis and its mechanism remain unknown. Previous work showed that human umbilical cord-MSCs (hucMSCs) transplanted into acutely injured and fibrotic livers could restore liver function and improve liver fibrosis. In this study, it was found that transplantation of exosomes derived from hucMSC (hucMSC-Ex) reduced the surface fibrous capsules and got their textures soft, alleviated hepatic inflammation and collagen deposition in carbon tetrachloride (CCl4)-induced fibrotic liver. hucMSC-Ex also significantly recovered serum aspartate aminotransferase (AST) activity, decreased collagen type I and III, transforming growth factor (TGF)-β1 and phosphorylation Smad2 expression in vivo. In further experiments, we found that epithelial-to-mesenchymal transition (EMT)-associated markers E-cadherin-positive cells increased and N-cadherin- and vimentin-positive cells decreased after hucMSC-Ex transplantation. Furthermore, the human liver cell line HL7702 underwent typical EMT after induction with recombinant human TGF-β1, and then hucMSC-Ex treatment reversed spindle-shaped and EMT-associated markers expression in vitro. Taken together, these results suggest that hucMSC-Ex could ameliorate CCl4-induced liver fibrosis by inhibiting EMT and protecting hepatocytes. This provides a novel approach for the treatment of fibrotic liver disease.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Tingfen
authors.initials: T
authors.lastname: Li
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Yan
authors.forename: Bingying
authors.initials: B
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002457:Cell Extracts / Q000627:therapeutic use*; D002460:Cell Line; D048430:Cell Shape; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000628:therapy*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D002457:Cell Extracts; D024042:Collagen Type I; D024061:Collagen Type III; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride