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Bone Marrow Mesenchymal Stem Cells Reverse Liver Damage in a Carbon Tetrachloride-induced Mouse Model of Chronic Liver Injury.
- Source :
-
In vivo (Athens, Greece) [In Vivo] 2016 May-Jun; Vol. 30 (3), pp. 187-93. - Publication Year :
- 2016
-
Abstract
- Background/aim: The aim of this study was to investigate the effect of bone-marrow mesenchymal stem cells (BMSCs) on repair of liver damage in a carbon tetrachloride (CCl4)-induced mouse model of chronic liver damage.<br />Materials and Methods: Green fluorescent protein (GFP)-expressing BMSCs, isolated from GFP transgenic mice, were transplanted into mice with chronic liver damage induced by CCl4 The GFP-expressing BMSCs in livers were detected by fluorescence microscopy. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured for assessment of liver function. Liver histopathology was performed to assess liver damage. mRNA and protein expression of liver-associated markers albumin (Alb) and alpha-fetoprotein (Afp) were detected to confirm the hepatic differentiation of BMSCs in the liver. Immunostaining for the expression of interleukin-10 (IL-10) and matrix metallopeptidase-9 (MMP-99), and enzyme-linked immunosorbent assay for the secretion of type III collagen and lamininin was carried out.<br />Results: After BMSC transplantation, GFP-expressing BMSCs were detected in the peri-portal and injured areas of the CCL4-injured liver. mRNA and protein expressions of Alb and Afp were significantly increased in BMSC-transplanted liver. Mice treated with BMSCs displayed reduced serum levels of ALT and AST, and CCl4-induced histopathological changes in livers were repaired. BMSC transplantation increased the production of IL-10 and inhibited the expression of MMP-9, as well as the secretion of type III collagen and lamininin.<br />Conclusion: BMSCs transplanted into mice can migrate into damaged liver, differentiate into hepatocytes and promote recovery from chemically-induced liver damage. Promotion of IL-10 and inhibition of MMP-9 by transplanted BMSCs may be involved in the anti-inflammatory and anti-fibrotic action of BMSCs.<br /> (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Subjects :
- Alanine Transaminase blood
Animals
Aspartate Aminotransferases blood
Carbon Tetrachloride toxicity
Cells, Cultured
Chemical and Drug Induced Liver Injury, Chronic etiology
Chemical and Drug Induced Liver Injury, Chronic genetics
Female
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Humans
Immunohistochemistry
Interleukin-10 metabolism
Liver metabolism
Liver pathology
Matrix Metalloproteinase 9 metabolism
Mesenchymal Stem Cells metabolism
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Reverse Transcriptase Polymerase Chain Reaction
alpha-Fetoproteins genetics
alpha-Fetoproteins metabolism
Chemical and Drug Induced Liver Injury, Chronic therapy
Disease Models, Animal
Mesenchymal Stem Cell Transplantation methods
Mesenchymal Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7549
- Volume :
- 30
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- In vivo (Athens, Greece)
- Publication Type :
- Academic Journal
- Accession number :
- 27107074