Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-20304-5
Title: Directed Differentiation of Adult Liver Derived Mesenchymal Like Stem Cells into Functional Hepatocytes
Authors: Luo X.
Gupta K. 
Ananthanarayanan A.
Wang Z.
Xia L. 
Li A.
Sakban R.B. 
Liu S.
Yu H. 
Keywords: biological marker
animal
cell culture
cell culture technique
cell differentiation
cell proliferation
cytology
flow cytometry
liver
liver cell
male
mesenchymal stem cell
metabolism
physiology
procedures
rat
stem cell
Wistar rat
Animals
Biomarkers
Cell Culture Techniques
Cell Differentiation
Cell Proliferation
Cells, Cultured
Flow Cytometry
Hepatocytes
Liver
Male
Mesenchymal Stem Cells
Rats
Rats, Wistar
Stem Cells
Issue Date: 2018
Citation: Luo X., Gupta K., Ananthanarayanan A., Wang Z., Xia L., Li A., Sakban R.B., Liu S., Yu H. (2018). Directed Differentiation of Adult Liver Derived Mesenchymal Like Stem Cells into Functional Hepatocytes. Scientific Reports 8 (1) : 2818. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-20304-5
Abstract: Shortage of functional hepatocytes hampers drug safety testing and therapeutic applications because mature hepatocytes cannot be expanded and maintain functions in vitro. Recent studies have reported that liver progenitor cells can originate from mature hepatocytes in vivo. Derivation of proliferating progenitor cells from mature hepatocytes, and re-differentiation into functional hepatocytes in vitro has not been successful. Here we report the derivation of novel mesenchymal-like stem cells (arHMSCs) from adult rat hepatocytes. Immunofluorescence and flow cytometry characterization of arHMSCs found expression of mesenchymal markers CD29, CD44, CD90, vimentin and alpha smooth muscle actin. These arHMSCs proliferated in vitro for 4 passages yielding 104 fold increase in cell number in 28 days, and differentiated into hepatocyte-like cells (arHMSC-H). The arHMSC-H expressed significantly higher level of hepatocyte-specific markers (200 fold for albumin and 6 fold for Cyp450 enzymes) than arHMSCs. The arHMSC-H also demonstrated dose response curves similar to primary hepatocytes for 3 of the 6 paradigm hepatotoxicants tested, demonstrating utility in drug safety testing applications. © 2018 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175029
ISSN: 20452322
DOI: 10.1038/s41598-018-20304-5
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