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Title: | Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice. | Authors: | Lourensz D.;Vaghjiani V.;Manuelpillai U.;Tchongue J.;Williams E.D.;Liu A.;Samuel C.S.;Sievert W. | Institution: | (Manuelpillai, Vaghjiani) Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia (Tchongue, Lourensz, Liu, Sievert) Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, VIC, Australia (Samuel) Howard Florey Institute, University of Melbourne, Melbourne, VIC, Australia (Samuel) Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC, Australia (Williams) Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia (Sievert) Gastroenterology and Hepatology Unit, Monash Medical Centre, Clayton, VIC, Australia | Issue Date: | 12-Oct-2012 | Copyright year: | 2010 | Publisher: | Cognizant Communication Corporation (3 Hartsdale Road, Elmsford NY 10523-3701, United States) | Place of publication: | United States | Publication information: | Cell Transplantation. 19 (9) (pp 1157-1168), 2010. Date of Publication: 2010. | Abstract: | Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Embryonic and mesenchymal stem cells have been shown to reduce experimental liver fibrosis but have potential limitations, including the formation of dysplastic precursors, tumors, and profibrogenic cells. Other stem-like cells may reduce hepatic inflammation and fibrosis without tumor and profibrogenic cell formation. To test this hypothesis we transplanted human amnion epithelial cells (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 of a 4-week regimen of carbon tetrachloride (CCl4) exposure to induce liver fibrosis. Two weeks following hAEC infusion, intact cells expressing the human-specific markers inner mitochondrial membrane protein and human leukocyte antigen-G were found in mouse liver without evidence of host rejection of the transplanted cells. Human albumin, known to be produced by hAEC, was detected in sera of hAEC-treated mice. Human DNA was detected in mouse liver and also spleen, lungs, and heart of some animals. Following hAEC transplantation, CCl4-treated animals showed decreased serum ALT levels and reduced hepatocyte apoptosis, compared to controls. hAEC-treated mouse liver had lower TNF-alpha and IL-6 protein levels and higher IL-10 compared to animals given CCl4 alone. Compared to CCl4 controls, hAEC-treated mice showed fewer activated collagen-producing hepatic stellate cells and less fibrosis area and collagen content. Reduced hepatic TGF-beta levels in conjunction with a twofold increase in the active form of the collagen-degrading enzyme matrix metalloproteinase-2 in hAEC-treated mice compared to CCl4 controls may account for the reduction in fibrosis. hAEC transplantation into immunocompetent mice leads to cell engraftment, reduced hepatocyte apoptosis, and decreased hepatic inflammation and fibrosis. All rights reserved. Copyright © 2010 Cognizant Comm. Corp. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.3727/096368910X504496 | PubMed URL: | 20447339 [http://www.ncbi.nlm.nih.gov/pubmed/?term=20447339] | ISSN: | 0963-6897 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/30977 | Type: | Article | Subjects: | mouse nonhuman placenta priority journal stellate cell alanine aminotransferase/ec [Endogenous Compound] *carbon tetrachloride/pd [Pharmacology] collagen/ec [Endogenous Compound] gelatinase A/ec [Endogenous Compound] interleukin 10/ec [Endogenous Compound] interleukin 6/ec [Endogenous Compound] leukocyte antigen/ec [Endogenous Compound] tumor necrosis factor alpha/ec [Endogenous Compound] liver cell *amnion cell animal cell animal experiment animal model animal tissue apoptosis article cell isolation *cell transplantation collagen degradation controlled study engraftment *epithelium cell hepatitis human human cell *immunocompetence *liver fibrosis male mitochondrial membrane engraftment *epithelium cell hepatitis human human cell *immunocompetence liver cell *liver fibrosis male mitochondrial membrane mouse animal experiment placenta priority journal stellate cell animal cell *amnion cell nonhuman animal model animal tissue apoptosis article cell isolation *cell transplantation collagen degradation controlled study |
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