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Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells
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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.

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|April 5, 2020
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Summary
This summary is machine-generated.

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.

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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.