Biofabricated 3D in vitro model of fibrosis-induced abnormal hepatoblast/biliary progenitors' expansion of the developing liver.
3D organoids
HepaRG
biliary development
fibrosis
hepatic stellate cell
Journal
Bioengineering & translational medicine
ISSN: 2380-6761
Titre abrégé: Bioeng Transl Med
Pays: United States
ID NLM: 101689146
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
16
09
2020
revised:
25
11
2020
accepted:
29
11
2020
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
1
10
2021
Statut:
epublish
Résumé
Congenital disorders of the biliary tract are the primary reason for pediatric liver failure and ultimately for pediatric liver transplant needs. Not all causes of these disorders are well understood, but it is known that liver fibrosis occurs in many of those afflicted. The goal of this study is to develop a simple yet robust model that recapitulates physico-mechanical and cellular aspects of fibrosis mediated via hepatic stellate cells (HSCs) and their effects on biliary progenitor cells. Liver organoids were fabricated by embedding various HSCs, with distinctive abilities to generate mild to severe fibrotic environments, together with undifferentiated liver progenitor cell line, HepaRG, within a collagen I hydrogel. The fibrotic state of each organoid was characterized by examination of extracellular matrix (ECM) remodeling through quantitative image analysis, rheometry, and qPCR. In tandem, the phenotype of the liver progenitor cell and cluster formation was assessed through histology. Activated HSCs (aHSCs) created a more severe fibrotic state, exemplified by a more highly contracted and rigid ECM, as well higher relative expression of
Identifiants
pubmed: 34589593
doi: 10.1002/btm2.10207
pii: BTM210207
pmc: PMC8459590
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e10207Informations de copyright
© 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.
Déclaration de conflit d'intérêts
The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Références
Methods Mol Med. 2005;117:237-50
pubmed: 16118456
Gut. 2005 Jan;54(1):142-51
pubmed: 15591520
Biotechnol Bioeng. 2020 Aug;117(8):2516-2526
pubmed: 32391915
Arch Pathol Lab Med. 2012 Jul;136(7):746-60
pubmed: 22742548
Hepatology. 1999 Aug;30(2):372-8
pubmed: 10421642
Sci Transl Med. 2014 Jul 16;6(245):245sr2
pubmed: 25031271
Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G110-8
pubmed: 21527725
Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):67-80
pubmed: 22149583
Sci Transl Med. 2015 May 6;7(286):286ra67
pubmed: 25947162
Gastroenterology. 2003 Jan;124(1):147-59
pubmed: 12512039
Hepatology. 2010 Feb;51(2):454-62
pubmed: 20101745
Oncotarget. 2016 Feb 2;7(5):6159-74
pubmed: 26716418
Hepatology. 2018 Feb;67(2):750-761
pubmed: 28834615
Methods Mol Biol. 2010;640:261-72
pubmed: 20645056
Int J Mol Sci. 2018 Mar 21;19(4):
pubmed: 29561796
Genes Dev. 1996 Jan 1;10(1):70-9
pubmed: 8557196
Acta Biomater. 2017 Dec;64:67-79
pubmed: 28966094
Development. 2003 Jun;130(11):2513-24
pubmed: 12702664
J Biomed Biotechnol. 2010;2010:984248
pubmed: 20169172
Tissue Eng Part A. 2017 Oct;23(19-20):1026-1041
pubmed: 28922975
Hepat Med. 2010 May 25;2:49-67
pubmed: 24367208
Development. 2009 May;136(10):1727-39
pubmed: 19369401
Am J Pathol. 2005 Apr;166(4):1077-88
pubmed: 15793288
Mol Biol Cell. 2007 Apr;18(4):1472-9
pubmed: 17314404
Liver Transpl. 2005 Feb;11(2):152-60
pubmed: 15666395
J Hepatol. 1985;1(5):489-99
pubmed: 4056351
Liver Transpl. 2012 Feb;18(2):226-37
pubmed: 22034152
Biomed Res Int. 2016;2016:2646212
pubmed: 27800489
Development. 2002 Feb;129(4):1075-82
pubmed: 11861489
Methods Mol Biol. 2017;1627:429-451
pubmed: 28836218
Am J Physiol Gastrointest Liver Physiol. 2015 May 15;308(10):G807-30
pubmed: 25767261
Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):296-306
pubmed: 19876928
Arch Pathol Lab Med. 2007 Nov;131(11):1728-34
pubmed: 17979495
FEBS Lett. 2007 Jan 23;581(2):203-10
pubmed: 17187782
ISRN Surg. 2012;2012:132089
pubmed: 23304557
Exp Pathol. 1988;34(4):229-36
pubmed: 2853079
Basic Clin Pharmacol Toxicol. 2017 Jan;120(1):30-37
pubmed: 27285124
Dev Biol. 2007 Dec 1;312(1):157-70
pubmed: 18028902
J Clin Invest. 2013 May;123(5):1902-10
pubmed: 23635788
Hepatology. 2014 Aug;60(2):700-14
pubmed: 24715669
Am J Pathol. 1998 Aug;153(2):527-35
pubmed: 9708812
Sci Rep. 2019 Dec 20;9(1):19601
pubmed: 31862949
Nat Rev Gastroenterol Hepatol. 2014 Feb;11(2):74
pubmed: 24322897
World J Gastroenterol. 2006 Dec 14;12(46):7413-20
pubmed: 17167827
J Clin Transl Hepatol. 2015 Mar;3(1):53-66
pubmed: 26357635
Elife. 2018 Dec 27;7:
pubmed: 30589410
J Biomed Opt. 2014 Jan;19(1):16007
pubmed: 24407500
Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
pubmed: 15573414
J Surg Res. 2017 Jul;215:250-256
pubmed: 28688656
Arch Toxicol. 2011 Feb;85(2):79-117
pubmed: 21225242
PLoS One. 2016 Mar 21;11(3):e0151736
pubmed: 26998606
Antioxid Redox Signal. 2014 Sep 1;21(7):1078-97
pubmed: 24219114
Am J Pathol. 2008 Dec;173(6):1818-27
pubmed: 18988804
Gastroenterology. 2004 Apr;126(4):1147-56
pubmed: 15057753
Exp Biol Med (Maywood). 2016 Sep;241(15):1684-98
pubmed: 27385595
Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):245-58
pubmed: 21497742
Dig Dis. 2016;34(4):347-55
pubmed: 27170388