Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds.
biomaterials, cholangiocyte morphogenesis
liver
microfluidics
morphogenesis
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
04
09
2021
received:
24
06
2021
pubmed:
18
11
2021
medline:
24
3
2022
entrez:
17
11
2021
Statut:
ppublish
Résumé
Patients with Alagille syndrome carry monogenic mutations in the Notch signaling pathway and face complications such as jaundice and cholestasis. Given the presence of intrahepatic ductopenia in these patients, Notch2 receptor signaling is implicated in driving normal biliary development and downstream branching morphogenesis. As a result, in vitro model systems of liver epithelium are needed to further mechanistic insight of biliary tissue assembly. Here, primary human intrahepatic cholangiocytes as a candidate population for such a platform are systematically evaluated, and conditions that direct their branching morphogenesis are described. It is found that extracellular matrix presentation, coupled with mitogen stimulation, promotes biliary branching in a Notch-dependent manner. These results demonstrate the utility of using 3D scaffolds for mechanistic investigation of cholangiocyte branching and provide a gateway to integrate biliary architecture in additional in vitro models of liver tissue.
Identifiants
pubmed: 34786888
doi: 10.1002/advs.202102698
pmc: PMC8787431
doi:
Substances chimiques
Biocompatible Materials
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2102698Subventions
Organisme : NIH HHS
ID : EB008396
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB008396
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB016652
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
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