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Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System
Published on: May 10, 2020
Human hepatic stem cells from fetal and postnatal donors
Eva Schmelzer1, Lili Zhang, Andrew Bruce
1Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
The Journal of Experimental Medicine
|August 1, 2007
Summary
Human hepatic stem cells (hHpSCs), identified by EpCAM+ markers, show self-renewal and differentiate into liver cells. These EpCAM+ cells are promising candidates for liver cell therapies.
Area of Science:
- Hepatology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Human hepatic stem cells (hHpSCs) are liver precursors found in fetal ductal plates and adult Canals of Hering.
- These cells are crucial for liver development and regeneration.
Purpose of the Study:
- To characterize human hepatic stem cells (hHpSCs) for their potential in liver cell therapies.
- To investigate the properties, markers, and differentiation capacity of hHpSCs.
Main Methods:
- Isolation of hHpSCs using immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells.
- In vitro expansion in serum-free defined medium, assessing self-renewal and doubling time.
- Characterization of cell surface markers and gene expression.
- In vivo transplantation into NOD/SCID mice to evaluate differentiation and tissue formation.
Main Results:
- hHpSCs were isolated as EpCAM+ cells, constituting 0.5-2.5% of liver parenchyma.
- Cells demonstrated stable phenotype after >150 population doublings, indicating self-renewal capacity.
- hHpSCs express specific markers (CK8, 18, 19, CD133/1, telomerase, CD44H, claudin 3, weak albumin) and lack markers of mature liver, hematopoietic, or mesenchymal cells.
- Transplantation into mice resulted in mature liver tissue expressing human proteins.
Conclusions:
- Human hepatic stem cells (hHpSCs) possess self-renewal and differentiation capabilities.
- EpCAM+ hHpSCs are a viable source for generating functional liver tissue.
- These cells hold significant potential for future liver cell-based therapies.
