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: Yan Liu, Xue Yang, Yingying Jing, Shanshan Zhang, Chen Zong, Jinghua Jiang, Kai Sun, Rong Li, Lu Gao, Xue Zhao, Dong Wu, Yufang Shi, Zhipeng Han, Lixin Wei
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 17762 (Dec 08 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26643997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL12
• Receptors, CXCR4
• Carbon Tetrachloride

Topics

• Animals
• Bone Marrow Cells (cytology, metabolism)
• Bone Marrow Transplantation
• Carbon Tetrachloride (adverse effects)
• Cell Movement
• Chemokine CXCL12 (metabolism)
• Disease Models, Animal
• Hematopoietic Stem Cell Mobilization (methods)
• Immunophenotyping
• Liver Cirrhosis (chemically induced, metabolism, pathology)
• Male
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Transgenic
• Phenotype
• Receptors, CXCR4 (metabolism)