In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors.
(2009) Translational Research : the journal of laboratory and clinical medicine — Vol. 154, n° 3, p. 122-132 (2009)
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- Abstract
- Recent findings demonstrated that stem cells could be harvested from a patient and used to repair his or her own damaged liver. Additionally, stem cells may be manipulated in vitro to induce hepatic differentiation. The current study aims to determine the differentiation efficacy of various liver-specific factors (hepatocyte growth factor, Insulin-Transferrin-Selenium, dexamethasone, and nicotinamide) used for stem cell differentiation into hepatocyte-like cells. Human mesenchymal stem cells were exposed to different media containing these compounds added individually or in various combinations. Hepatic differentiation was assessed via quantitative reverse transcription-polymerase chain reaction and immunocytochemical staining for stemness or liver-specific genes and proteins, including albumin, cytokeratins 18 and 19, HepPar-1, alpha-fetoprotein, and nestin. In addition, functional tests for glycogen storage, urea production, glucose, and albumin synthesis were also performed. The expression profiles of albumin, alpha-fetoprotein, and cytokeratin 19 demonstrated that when hepatocyte growth factor, nicotinamide, or dexamethasone were added individually, incomplete hepatocyte differentiation was achieved; the obtained cell populations contained progenitors that expressed both hepatic (albumin) and biliary (cytokeratin 19) markers, as well as alpha-fetoprotein. Hepatocyte growth factor and nicotinamide were the factors with the most hepatogenic potential. When all factors were added to the culture, cells exhibited features that closely resembled human adult hepatocytes as determined by their gene expression patterns (albumin, HepPar-1, and alpha-fetoprotein, but not cytokeratin 19) and functional testing. These cells with hepatic function may become important tools for liver transplant procedures, liver development studies, and pharmacologic research.
- Affiliations
Stefan S. Nicolau Institute of Virology, Bucharest, Romania Department of Antiviral Therapy Fundeni Clinical Institute of Digestive Disease and Liver Transplantation, Bucharest, Romania Digestive Disease and Liver Transplantation Victor Babes National Institute for Research and Development in Pathology and Biomedical Sciences, Bucharest, Romania Research and Development in Pathology and Biomedical Sciences Fundeni Clinical Institute, Bucharest, Romania Department of Haematology
Citations
Chivu, M., Dima, S. O., Stancu, I.-C., Dobrea, C., Uscatescu, V., Necula, L. G., Bleotu, C., Tanase, C., Albulescu, R., Ardeleanu, C., & Popescu, I. (2009). In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors. Translational Research : the journal of laboratory and clinical medicine, 154(3), 122-132. https://doi.org/10.1016/j.trsl.2009.05.007 (Original work published 2009)