Expansion, in vivo-ex vivo cycling, and genetic manipulation of primary human hepatocytes.
Animals
Cell Transplantation
Chimera
Disease Models, Animal
Female
Genetic Therapy
Hepatitis B
Hepatitis B virus
Hepatocytes
/ drug effects
Homeodomain Proteins
/ genetics
Humans
Hydrolases
/ genetics
Interleukin Receptor Common gamma Subunit
/ genetics
Liver
/ pathology
Liver Diseases
/ genetics
Malaria
Male
Mice
Mice, Inbred NOD
Mice, Knockout
Plasmodium falciparum
Pyrrolizidine Alkaloids
/ pharmacology
hepatitis B virus
hepatotropic pathogens
humanized mice
liver
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
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
1678-1688Subventions
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.
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