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Factors affecting hepatocyte isolation, engraftment, and replication in an in vivo model
Author(s) -
Kawahara Toshiyasu,
Toso Christian,
Douglas Don.,
Nourbakhsh Mahra,
Lewis Jamie T.,
Tyrrell David Lorne,
Lund Garry A.,
Churchill Thomas A.,
Kneteman Norman M.
Publication year - 2010
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.22099
Subject(s) - medicine , hepatocyte , liver transplantation , transplantation , albumin , in vivo , bioartificial liver device , ischemia , andrology , immunology , in vitro , biology , microbiology and biotechnology , biochemistry
Human hepatocyte transplantation is an alternative treatment for acute liver failure and liver diseases involving enzyme deficiencies. Although it has been successfully applied in selected recipients, both isolation and transplantation outcomes have the potential to be improved by better donor selection. This study assessed the impact of various donor variables on isolation outcomes (yield and viability) and posttransplant engraftment, using the SCID/Alb‐uPA (severe combined immunodeficient/urokinase type plasminogen activator under the control of an albumin promoter) human liver chimeric mouse model. Human hepatocytes were obtained from 90 human liver donor specimens and were transplanted into 3942 mice. Multivariate analysis revealed improved viability with younger donors ( P = 0.038) as well as with shorter warm ischemic time ( P = 0.012). Hepatocyte engraftment, assessed by the posttransplant level of serum human α1‐antitrypsin, was improved with shorter warm ischemia time. Hepatocytes isolated from older donors (≥60 years) had lower viability and posttransplant engraftment ( P ≤ 0.01). In conclusion, the selection of young donors (<60 years) and rapid liver specimen retrieval, allowing for shorter warm ischemia time, are key determinants for the success of both the isolation of high viability human hepatocytes and their subsequent posttransplantation capacity for engraftment and expansion. Liver Transpl 16:974‐982, 2010. © 2010 AASLD.