PMID- 17664939
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20240104
IS  - 1087-0156 (Print)
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Linking)
VI  - 25
IP  - 8
DP  - 2007 Aug
TI  - Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice.
PG  - 903-10
AB  - Mice that could be highly repopulated with human hepatocytes would have many 
      potential uses in drug development and research applications. The best available 
      model of liver humanization, the uroplasminogen-activator transgenic model, has 
      major practical limitations. To provide a broadly useful hepatic xenorepopulation 
      system, we generated severely immunodeficient, fumarylacetoacetate hydrolase 
      (Fah)-deficient mice. After pretreatment with a urokinase-expressing adenovirus, 
      these animals could be highly engrafted (up to 90%) with human hepatocytes from 
      multiple sources, including liver biopsies. Furthermore, human cells could be 
      serially transplanted from primary donors and repopulate the liver for at least 
      four sequential rounds. The expanded cells displayed typical human drug 
      metabolism. This system provides a robust platform to produce high-quality human 
      hepatocytes for tissue culture. It may also be useful for testing the toxicity of 
      drug metabolites and for evaluating pathogens dependent on human liver cells for 
      replication.
FAU - Azuma, Hisaya
AU  - Azuma H
AD  - Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 
      97239, USA.
FAU - Paulk, Nicole
AU  - Paulk N
FAU - Ranade, Aarati
AU  - Ranade A
FAU - Dorrell, Craig
AU  - Dorrell C
FAU - Al-Dhalimy, Muhsen
AU  - Al-Dhalimy M
FAU - Ellis, Ewa
AU  - Ellis E
FAU - Strom, Stephen
AU  - Strom S
FAU - Kay, Mark A
AU  - Kay MA
FAU - Finegold, Milton
AU  - Finegold M
FAU - Grompe, Markus
AU  - Grompe M
LA  - eng
GR  - F31 CA130116/CA/NCI NIH HHS/United States
GR  - R01-DK48252/DK/NIDDK NIH HHS/United States
GR  - DK 92310/DK/NIDDK NIH HHS/United States
GR  - GM 06346/GM/NIGMS NIH HHS/United States
GR  - N01DK92310/LM/NLM NIH HHS/United States
GR  - R01 DK048252/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070729
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Il2rg protein, mouse)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (Rag2 protein, mouse)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.7.1.2 (fumarylacetoacetase)
SB  - IM
CIN - Nat Biotechnol. 2007 Aug;25(8):871-2. PMID: 17687361
MH  - Animals
MH  - Cell Culture Techniques/*methods
MH  - DNA-Binding Proteins/*genetics
MH  - Hepatocytes/*cytology/*transplantation
MH  - Humans
MH  - Hydrolases/*genetics
MH  - Interleukin Receptor Common gamma Subunit/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Tissue Engineering/*methods
PMC - PMC3404624
MID - NIHMS389426
EDAT- 2007/08/01 09:00
MHDA- 2007/11/14 09:00
PMCR- 2012/07/25
CRDT- 2007/08/01 09:00
PHST- 2007/03/15 00:00 [received]
PHST- 2007/07/13 00:00 [accepted]
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
PHST- 2012/07/25 00:00 [pmc-release]
AID - nbt1326 [pii]
AID - 10.1038/nbt1326 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2007 Aug;25(8):903-10. doi: 10.1038/nbt1326. Epub 2007 Jul 29.