Stem cell-derived polarized hepatocytes.
Nat Commun
; 11(1): 1677, 2020 04 03.
Article
in En
| MEDLINE
| ID: mdl-32245952
ABSTRACT
Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined basolateral and apical membranes separated by tight junctions. We show that polarized HLCs secrete cargo directionally Albumin, urea, and lipoproteins are secreted basolaterally, whereas bile acids are secreted apically. Further, we show that enterically transmitted hepatitis E virus (HEV) progeny particles are secreted basolaterally as quasi-enveloped particles and apically as naked virions, recapitulating essential steps of the natural infectious cycle in vivo. We also provide proof-of-concept that polarized HLCs can be used for pharmacokinetic and drug-drug interaction studies. This novel system provides a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism in a more physiologically relevant setting.
Full text:
1
Database:
MEDLINE
Main subject:
Cell Polarity
/
Cell Culture Techniques
/
Hepatocytes
/
Induced Pluripotent Stem Cells
Type of study:
Prognostic_studies
Language:
En
Journal:
Nat Commun
Year:
2020
Type:
Article
Affiliation country:
United States