Human Multilineage 3D Spheroids as a Model of Liver Steatosis and Fibrosis.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
02 Apr 2019
Historique:
received: 25 02 2019
revised: 29 03 2019
accepted: 30 03 2019
entrez: 17 4 2019
pubmed: 17 4 2019
medline: 31 7 2019
Statut: epublish

Résumé

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. Despite the high prevalence of NAFLD, the underlying biology of the disease progression is not clear, and there are no approved drugs to treat non-alcoholic steatohepatitis (NASH), the most advanced form of the disease. Thus, there is an urgent need for developing advanced in vitro human cellular systems to study disease mechanisms and drug responses. We attempted to create an organoid system genetically predisposed to NAFLD and to induce steatosis and fibrosis in it by adding free fatty acids. We used multilineage 3D spheroids composed by hepatocytes (HepG2) and hepatic stellate cells (LX-2) with a physiological ratio (24:1). HepG2 and LX-2 cells are homozygotes for the

Identifiants

pubmed: 30986904
pii: ijms20071629
doi: 10.3390/ijms20071629
pmc: PMC6480107
pii:
doi:

Substances chimiques

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid 0
Apolipoproteins B 0
Chalcones 0
Collagen Type I 0
Fatty Acids 0
Propionates 0
Liraglutide 839I73S42A

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Vetenskapsrådet
ID : 2016-01527
Organisme : Hjärt-Lungfonden
ID : 20120533
Organisme : the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement
ID : SU 2018-04276
Organisme : Novonordisk Foundation Grant for Excellence in Endocrinology
ID : Excellence Project, 9321-430
Organisme : Swedish Diabetes Foundation
ID : DIA 2017-205
Organisme : Research grant from AstraZeneca
ID : Echo Project, 10033852
Organisme : Wallenberg Academy Fellows from the Knut and Alice Wallenberg Foundation
ID : KAW 2017.0203

Références

Biochim Biophys Acta. 2004 Jul 5;1683(1-3):33-7
pubmed: 15238217
Dig Liver Dis. 2005 May;37(5):349-56
pubmed: 15843085
Hepatology. 2005 Jun;41(6):1313-21
pubmed: 15915461
Diabetologia. 2006 Apr;49(4):755-65
pubmed: 16463046
Toxicol In Vitro. 2007 Jun;21(4):545-57
pubmed: 17289342
Gastroenterology. 2007 May;132(5):1937-46
pubmed: 17484886
Nat Rev Mol Cell Biol. 2007 Oct;8(10):839-45
pubmed: 17684528
Nat Med. 2007 Nov;13(11):1324-32
pubmed: 17952090
Arch Pathol Lab Med. 2007 Nov;131(11):1728-34
pubmed: 17979495
Physiol Rev. 2008 Jan;88(1):125-72
pubmed: 18195085
Oncol Rep. 2008 Dec;20(6):1465-71
pubmed: 19020729
Genes Nutr. 2009 Mar;4(1):13-22
pubmed: 19104883
Fibrogenesis Tissue Repair. 2010 Feb 17;3:3
pubmed: 20163708
Hepatology. 2010 May;51(5):1584-92
pubmed: 20225248
Trends Cell Biol. 2011 Dec;21(12):745-54
pubmed: 22033488
BMC Gastroenterol. 2012 Mar 01;12:20
pubmed: 22380754
Cell Metab. 2012 May 2;15(5):691-702
pubmed: 22560221
J Hepatol. 2012 Dec;57(6):1276-82
pubmed: 22878467
Hepatology. 2013 May;57(5):1763-72
pubmed: 23175050
J Hepatol. 2013 Mar;58(3):593-608
pubmed: 23419824
PLoS One. 2013;8(4):e60335
pubmed: 23560091
J Clin Invest. 2013 May;123(5):1902-10
pubmed: 23635788
Am J Pathol. 1990 Jul;137(1):59-70
pubmed: 2372043
Diabetes. 2014 Jan;63(1):312-22
pubmed: 24009255
Hum Mol Genet. 2014 Aug 1;23(15):4077-85
pubmed: 24670599
Nature. 2014 Jun 5;510(7503):47
pubmed: 24899303
Lancet. 2015 Mar 14;385(9972):956-65
pubmed: 25468160
Exp Mol Pathol. 2015 Feb;98(1):85-92
pubmed: 25533546
J Hepatol. 2015 Jul;63(1):141-7
pubmed: 25678385
J Hepatol. 2015 Sep;63(3):705-12
pubmed: 25980762
J Nutr. 2015 Aug;145(8):1687-91
pubmed: 26136587
Toxicol In Vitro. 2015 Oct;29(7):1753-8
pubmed: 26187275
J Hepatol. 2015 Dec;63(6):1476-83
pubmed: 26272871
J Clin Endocrinol Metab. 2015 Dec;100(12):E1568-74
pubmed: 26439088
Lancet. 2016 Feb 13;387(10019):679-90
pubmed: 26608256
Hepatology. 2016 Jul;64(1):73-84
pubmed: 26707365
Gastroenterology. 2016 May;150(5):1147-1159.e5
pubmed: 26874076
Nat Rev Dis Primers. 2015 Dec 17;1:15080
pubmed: 27188459
Curr Protoc Mouse Biol. 2016 Jun 01;6(2):185-200
pubmed: 27248434
Nutr Metab (Lond). 2016 Sep 26;13:62
pubmed: 27708682
Hum Mol Genet. 2016 Dec 1;25(23):5212-5222
pubmed: 27742777
Sci Rep. 2016 Nov 17;6:36750
pubmed: 27853186
Clin Pharmacol Ther. 2017 Jul;102(1):131-140
pubmed: 28090653
Hepatology. 2017 May;65(5):1557-1565
pubmed: 28130788
Dis Model Mech. 2017 Jun 1;10(6):751-760
pubmed: 28331057
Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):397-411
pubmed: 28487545
J Exp Biol. 2017 Jul 15;220(Pt 14):2645-2653
pubmed: 28495868
Proteomics Clin Appl. 2018 Jan;12(1):
pubmed: 29105359
Expert Opin Drug Discov. 2018 Feb;13(2):193-205
pubmed: 29190166
J Intern Med. 2018 Apr;283(4):356-370
pubmed: 29280273
Antioxidants (Basel). 2018 Jan 16;7(1):
pubmed: 29337849
World J Gastroenterol. 2018 Jan 14;24(2):179-194
pubmed: 29375204
Annu Rev Pathol. 2018 Jan 24;13:321-350
pubmed: 29414249
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6):900-906
pubmed: 29935383
J Clin Lipidol. 2018 Nov - Dec;12(6):1390-1403.e4
pubmed: 30197273
Sci Rep. 2018 Sep 24;8(1):14297
pubmed: 30250238
Mol Metab. 2019 Apr;22:49-61
pubmed: 30772256
Hepatology. 1993 Feb;17(2):287-92
pubmed: 8428727
J Hepatol. 1996 Nov;25(5):677-83
pubmed: 8938545
Prog Liver Dis. 1996;14:101-30
pubmed: 9055576
J Clin Invest. 1998 Sep 1;102(5):910-8
pubmed: 9727059

Auteurs

Piero Pingitore (P)

Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. piero.pingitore@wlab.gu.se.

Kavitha Sasidharan (K)

Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. kavitha.sasidharan@wlab.gu.se.

Matias Ekstrand (M)

Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. matias.ekstrand@wlab.gu.se.

Sebastian Prill (S)

Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, SE-431 83 Gothenburg, Sweden. sebastian.prill@astrazeneca.com.

Daniel Lindén (D)

Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, SE-431 83 Gothenburg, Sweden. Daniel.Linden@astrazeneca.com.
Division of Endocrinology, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Daniel.Linden@astrazeneca.com.

Stefano Romeo (S)

Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. stefano.romeo@wlab.gu.se.
Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy. stefano.romeo@wlab.gu.se.
Cardiology Department, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. stefano.romeo@wlab.gu.se.

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Classifications MeSH