Differential fibrotic phenotypes of hepatic stellate cells within 3D liver organoids.
ECM remodeling
activated hepatic stellate cell
collagen fiber analysis
liver fibrosis
tissue stiffness
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
09
01
2020
revised:
16
04
2020
accepted:
07
05
2020
pubmed:
12
5
2020
medline:
11
8
2021
entrez:
12
5
2020
Statut:
ppublish
Résumé
Liver fibrosis occurs in most cases of chronic liver disease, which are somewhat common, but also a potentially deadly group of diseases. In vitro modeling of liver fibrosis relies primarily on the isolation of in vivo activated hepatic stellate cells (aHSCs) and studying them in standard tissue culture dishes (two-dimensional [2D]). In contrast, modeling of fibrosis in a biofabricated three-dimensional (3D) construct allows us to study changes to the environment, such as extracellular matrix (ECM) composition and structure, and tissue rigidity. In the current study, we used aHSCs produced through subcultures in 2D and encapsulated them in a 3D collagen gel to form spherical constructs. In parallel, and as a comparison, we used an established HSC line, LX-2, representing early and less severe fibrosis. Compared with LX-2 cells, the aHSCs created a stiffer environment and expressed higher levels of TIMP1 and LOXL2, all of which are indicative of advanced liver fibrosis. Collectively, this study presents a fibrosis model that could be incorporated with multi-cellular models to more accurately reflect the effects of a severe fibrotic environment on liver function.
Identifiants
pubmed: 32391915
doi: 10.1002/bit.27379
pmc: PMC7370813
mid: NIHMS1603516
doi:
Substances chimiques
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2516-2526Subventions
Organisme : NIBIB NIH HHS
ID : T32 EB014836
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA202822
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA180149
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
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