In vitro Hepatic Differentiation of Human Mesenchymal Stem Cells
Open accessAbstract
This study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from embryonic mesoderm, are able to differentiate into functional hepatocyte–like cells in vitro . MSCs were isolated from human bone marrow and umbilical cord blood, and the surface phenotype and the mesodermal multilineage differentiation potentials of these cells were characterized and tested. To effectively induce hepatic differentiation, we designed a novel 2–step protocol with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time–dependent manner. Differentiated cells further demonstrated in vitro functions characteristic of liver cells, including albumin production, glycogen storage, urea secretion, uptake of low–density lipoprotein, and phenobarbital–inducible cytochrome P450 activity. In conclusion , human MSCs from different sources are able to differentiate into functional hepatocyte–like cells and, hence, may serve as a cell source for tissue engineering and cell therapy of hepatic tissues. Furthermore, the broad differentiation potential of MSCs indicates that a revision of the definition may be required. (Hepatology 2004;40:1275-1284.)
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Recent studies have shown that MSCs can differentiate into ectodermal and endodermal cell lineages, beyond their mesodermal origin.
“The differentiation potential of MSCs was long thought to be limited to the germ layer of their origin (mesoderm), but recent studies have shown that they can also differentiate into ectodermal and endodermal cell lineages [88].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [88]
Human bone marrow-derived MSCs and umbilical cord blood-derived MSCs can differentiate into HLCs in vitro with morphology, phenotype, and functions characteristic of hepatocytes.
“Lee et al. found that human bone marrow-derived MSCs (BM-hMSCs) and umbilical cord blood-derived MSCs (UCB-MSCs) were able to differentiate into HLCs in vitro, with morphology, phenotype, and functions characteristic of hepatocytes [88].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [88]
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- Authors
- Lee, K., Kuo, T. K., Whang–Peng, J., Chung, Y., Lin, C., Chou, S., Chen, J., Chen, Y., & Lee, O. K.
- Affiliations
- National Health Research Institutes (TW)
- Fu Jen Catholic University (TW)
- Chang Gung University (TW)
- Corresponding author
- Lee, Oscar Kuang–Sheng
- Venue
- Hepatology
- Published
- 2004-12
- Volume
- 40
- Issue
- 6
- Pages
- 1275-1284
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1980776838
- Cited by
- 865
- References
- 1
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 19 · 2022: 11 · 2021: 29 · 2020: 33 · 2019: 30 · 2018: 33 · 2017: 30 · 2016: 40 · 2015: 51 · 2014: 67 · 2013: 66 · 2012: 67
- FWCI
- 24.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health Research Institutes
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- mesenchymal stem cells, hepatic differentiation, hepatocyte-like cells, bone marrow-derived stem cells, umbilical cord blood stem cells, hepatocyte growth factor, oncostatin M, multilineage differentiation, albumin synthesis, cytochrome P450 induction, liver tissue engineering
- MeSH terms
- Antigens, Bile Canaliculi, Cell Differentiation, Fetal Blood, Hematopoietic Stem Cells, Humans, Mesoderm, Biomarkers, Hepatocytes, In Vitro Techniques
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