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Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells
Published on: March 2, 2017
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Stem cell-derived polarized hepatocytes
Viet Loan Dao Thi1,2, Xianfang Wu3, Rachel L Belote4,5
1Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY, USA. VietLoan.DaoThi@med.uni-heidelberg.de.
Nature Communications
|April 5, 2020
Summary
Researchers developed a new method using transwell filters to create polarized human stem cell-derived hepatocyte-like cells (HLCs). These polarized HLCs mimic in vivo liver functions, enabling better studies of liver biology and drug metabolism.
Area of Science:
- Hepatology
- Stem Cell Biology
- Cell Polarity
Background:
- Human stem cell-derived hepatocyte-like cells (HLCs) are valuable for liver research.
- A key limitation of current HLCs is their lack of in vivo cell polarity.
Purpose of the Study:
- To develop a protocol for generating polarized HLCs.
- To characterize the in vivo-like functions of these polarized HLCs.
Main Methods:
- Utilized transwell filters in a stem cell differentiation protocol.
- Generated columnar polarized HLCs with distinct apical and basolateral membranes and tight junctions.
Main Results:
- Polarized HLCs exhibit directional secretion of albumin, urea, lipoproteins (basolateral), and bile acids (apical).
- Demonstrated recapitulation of hepatitis E virus (HEV) infectious cycle, with directional secretion of viral particles.
- Established proof-of-concept for using polarized HLCs in pharmacokinetic and drug-drug interaction studies.
Conclusions:
- This novel system generates physiologically relevant polarized HLCs.
- Offers a powerful tool for studying hepatocyte biology, liver diseases, and drug metabolism.
