Expansion, in vivo-ex vivo cycling, and genetic manipulation of primary human hepatocytes.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
21 01 2020
Historique:
pubmed: 10 1 2020
medline: 28 4 2020
entrez: 10 1 2020
Statut: ppublish

Résumé

Primary human hepatocytes (PHHs) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture, and resistance to genetic manipulation have limited their use. Here, we show that the pyrrolizidine alkaloid retrorsine improves PHH repopulation of chimeric mice on average 10-fold and rescues the ability of even poorly plateable donor hepatocytes to provide cells for subsequent ex vivo cultures. These mouse-passaged (mp) PHH cultures overcome the marked donor-to-donor variability of cryopreserved PHH and remain functional for months as demonstrated by metabolic assays and infection with hepatitis B virus and

Identifiants

pubmed: 31915293
pii: 1919035117
doi: 10.1073/pnas.1919035117
pmc: PMC6983380
doi:

Substances chimiques

Homeodomain Proteins 0
Il2rg protein, mouse 0
Interleukin Receptor Common gamma Subunit 0
Pyrrolizidine Alkaloids 0
RAG-1 protein 128559-51-3
Hydrolases EC 3.-
fumarylacetoacetase EC 3.7.1.2
retrorsine XJ86XWL8IY

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

1678-1688

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL131093
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK107164
Pays : United States
Organisme : Medical Research Council
ID : MR/K017047/1
Pays : United Kingdom
Organisme : NIAAA NIH HHS
ID : R01 AA027327
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK090576
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143295
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK085713
Pays : United States

Informations de copyright

Copyright © 2020 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

Références

Am J Pathol. 1998 Jul;153(1):319-29
pubmed: 9665494
Biochem Biophys Res Commun. 2011 Feb 18;405(3):405-10
pubmed: 21238430
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20507-11
pubmed: 18077355
Genes Dev. 1993 Dec;7(12A):2298-307
pubmed: 8253378
Hepatology. 2005 Apr;41(4):847-56
pubmed: 15791625
Cell Mol Gastroenterol Hepatol. 2017 Nov 22;5(2):131-144
pubmed: 29322086
Sci Transl Med. 2014 Sep 17;6(254):254ra129
pubmed: 25232181
Chem Biol Interact. 1973 Apr;6(4):207-18
pubmed: 4704120
J Clin Invest. 2010 Mar;120(3):924-30
pubmed: 20179355
Nat Rev Drug Discov. 2005 Jun;4(6):489-99
pubmed: 15931258
Tissue Eng Part A. 2016 May;22(9-10):742-53
pubmed: 27068494
Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15714-9
pubmed: 19720996
Nat Methods. 2017 Jul;14(7):687-690
pubmed: 28581496
J Hepatol. 2016 Aug;65(2):334-43
pubmed: 27151182
Gastroenterology. 2018 Apr;154(5):1258-1272
pubmed: 29428334
Am J Pathol. 2015 May;185(5):1275-85
pubmed: 25791527
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Antimicrob Agents Chemother. 2012 Aug;56(8):4277-88
pubmed: 22644022
Nat Biotechnol. 2007 Aug;25(8):903-10
pubmed: 17664939
Hepatology. 2019 Mar;69(3):1306-1316
pubmed: 30251414
Nature. 2017 Jul 20;547(7663):350-354
pubmed: 28700576
Gastroenterology. 2014 Apr;146(4):1070-83
pubmed: 24361467
Nat Med. 2001 Aug;7(8):927-33
pubmed: 11479625
Nat Genet. 1995 Aug;10(4):453-60
pubmed: 7545495
Nat Biotechnol. 2015 Dec;33(12):1264-1271
pubmed: 26501953
World J Gastroenterol. 2006 Mar 7;12(9):1439-42
pubmed: 16552817
Cell Res. 2019 Jan;29(1):8-22
pubmed: 30361550
Chem Biol Interact. 1975 Mar;10(3):185-97
pubmed: 1126005
J Hepatol. 2003 Sep;39(3):365-73
pubmed: 12927922
Sci Rep. 2017 Nov 30;7(1):16616
pubmed: 29192196
Mol Ther. 2016 Jun;24(6):1042-1049
pubmed: 27019999
Cell. 2018 Nov 29;175(6):1591-1606.e19
pubmed: 30500538
Drug Metab Pharmacokinet. 2005 Apr;20(2):121-6
pubmed: 15855724
Hepatology. 2011 Dec;54(6):1901-12
pubmed: 22144107

Auteurs

Eleftherios Michailidis (E)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Koen Vercauteren (K)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Laboratory of Liver Infectious Diseases, Ghent University, 9000 Ghent, Belgium.

Liliana Mancio-Silva (L)

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142.

Linda Andrus (L)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Cyprien Jahan (C)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Département de Biologie, Ecole Normale Supérieure Paris-Saclay, Université Paris-Saclay, 9423 Cachan, France.

Inna Ricardo-Lax (I)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Chenhui Zou (C)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10065.

Mohammad Kabbani (M)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Paul Park (P)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Department of Molecular Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Corrine Quirk (C)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Christina Pyrgaki (C)

Bio-Imaging Resource Center, The Rockefeller University, New York, NY 10065.

Brandon Razooky (B)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Lieven Verhoye (L)

Laboratory of Liver Infectious Diseases, Ghent University, 9000 Ghent, Belgium.

Irene Zoluthkin (I)

Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607.

Wei-Yu Lu (WY)

Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.

Stuart J Forbes (SJ)

Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.

Luis Chiriboga (L)

Department of Pathology, NYU Langone Health, New York, NY 10003.

Neil D Theise (ND)

Department of Pathology, NYU Langone Health, New York, NY 10003.

Roland W Herzog (RW)

Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607.
Herman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202.

Hiroshi Suemizu (H)

Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan.

William M Schneider (WM)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.

Amir Shlomai (A)

Department of Medicine D and the Liver Institute, Rabin Medical Center, Belinson Hospital, Petach-Tikva 49100, Israel.
Department of Gastroenterology and Liver Disease, Sackler Faculty of Medcine, Tel Aviv University, Tel Aviv 64239, Israel.

Philip Meuleman (P)

Laboratory of Liver Infectious Diseases, Ghent University, 9000 Ghent, Belgium.

Sangeeta N Bhatia (SN)

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142.
Broad Institute of MIT and Harvard, Cambridge, MA 02139.
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
Marble Center for Cancer Nanomedicine, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.

Charles M Rice (CM)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065; ricec@rockefeller.edu ydj2001@med.cornell.edu.

Ype P de Jong (YP)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065; ricec@rockefeller.edu ydj2001@med.cornell.edu.
Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10065.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH