title: Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis.
abstract: Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell-derived factor-1 (SDF-1α)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occurred when the expression balance of SDF-1α between liver and BM was disrupted, where SDF-1α expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zong
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Central laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Central laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Health Sciences and Shanghai Institute of Immunology, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, 225 South Chongqing Road, Shanghai 200225, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D016130:Immunophenotyping; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D002251:Carbon Tetrachloride