Brief Article
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World J Gastroenterol. Oct 28, 2010; 16(40): 5092-5103
Published online Oct 28, 2010. doi: 10.3748/wjg.v16.i40.5092
HNF-4α determines hepatic differentiation of human mesenchymal stem cells from bone marrow
Mong-Liang Chen, Kuan-Der Lee, Huei-Chun Huang, Yue-Lin Tsai, Yi-Chieh Wu, Tzer-Min Kuo, Cheng-Po Hu, Chungming Chang
Mong-Liang Chen, Huei-Chun Huang, Yue-Lin Tsai, Yi-Chieh Wu, Tzer-Min Kuo, Chungming Chang, Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan
Kuan-Der Lee, Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi 600, Taiwan
Tzer-Min Kuo, Chungming Chang, Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
Cheng-Po Hu, Department of Life Science, Tunghai University, Taichung 406, Taiwan
Author contributions: Chen ML and Lee KD contributed equally to this work; Chen ML, Lee KD, Hu CP and Chang C designed the research; Huang HC, Tsai YL, Wu YC and Kuo TM performed the research; Chen ML, Lee KD and Chang C analyzed the data and wrote the paper.
Supported by Grant MG-098-PP-08 from the National Health Research Institutes, Taiwan
Correspondence to: Dr. Chungming Chang, Distinguished Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.
Telephone: +886-37-246166 Fax: +886-37-586463
Received: May 18, 2010
Revised: July 6, 2010
Accepted: July 13, 2010
Published online: October 28, 2010

AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs).

METHODS: Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods.

RESULTS: Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF-4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes.

CONCLUSION: Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.

Keywords: Bone marrow, Cytochrome P450 genes, Differentiation of hepatocyte, Hepatocyte nuclear factor 4, Human mesenchymal stem cells