Prolonged engraftment of human hepatocytes in mice transgenic for the deleted form of human hepatocyte growth factor

Anuradha Krishnan, Kimberly Viker, Heleen Rietema, Marije Telgenkamp, Bruce Knudsen, Michael Charlton

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aim: Small animal models chimeric for human hepatocytes have provided valuable insights into the biology of hepatotropic viral infection and provided a platform for the study of therapeutic agents. Existing models of human hepatocyte transplantation are limited by phenotypic fragility and impaired immunity. We hypothesized that mice transgenic for human hepatocyte growth factor (HGF), a potent human hepatocyte mitogen, would engraft human hepatocytes in the absence of immunodeficiency. Methods: A plasmid construct containing the 2.3 kb coding region of the 723 amino acid isoform of HGF cDNA under the transcriptional control of the mouse albumin promoter/enhancer was used to generate transgenic mice. Cryopreserved human hepatocytes were transplanted into nine transgenic and six non-transgenic mice. Engraftment of human hepatocytes was followed for a period of 12 weeks by immunoblotting for human albumin in mouse serum samples. Results: In six out of the nine transgenic mice, abundance of human albumin, following an initial decline, increased andpeaked at > 70 days post transplantation, demonstrating sustained engraftment of transplanted human hepatocytes. In all the non-transgenic mice, post-transplant human albumin levels declined sequentially without evidence of sustained engraftment. Immunostaining of mouse liver sections indicated the presence of human hepatocytes adjacent to clusters of non-staining murine hepatocytes. Conclusion: These results demonstrate that sustained engraftment of human hepatocytes in mice is facilitated by expression of the human dHGF transgene. Human hepatocyte engraftment in this model has been achieved on an immunocompetent strain background and merits further study as a candidate for the study of hepatotropic viral infections.

Original languageEnglish (US)
Pages (from-to)854-862
Number of pages9
JournalHepatology Research
Volume37
Issue number10
DOIs
StatePublished - Oct 2007

Fingerprint

Transgenic Mice
Hepatocytes
Albumins
Virus Diseases
human HGF protein
Transplantation
Hepatocyte Growth Factor
Transgenes
Mitogens
Immunoblotting
Immunity
Protein Isoforms
Plasmids
Animal Models
Complementary DNA
Transplants
Amino Acids

Keywords

  • Deleted hepatocyte growth factor transgenic mouse
  • Engraftment
  • Human-mouse chimeric liver

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Prolonged engraftment of human hepatocytes in mice transgenic for the deleted form of human hepatocyte growth factor. / Krishnan, Anuradha; Viker, Kimberly; Rietema, Heleen; Telgenkamp, Marije; Knudsen, Bruce; Charlton, Michael.

In: Hepatology Research, Vol. 37, No. 10, 10.2007, p. 854-862.

Research output: Contribution to journalArticle

Krishnan, Anuradha ; Viker, Kimberly ; Rietema, Heleen ; Telgenkamp, Marije ; Knudsen, Bruce ; Charlton, Michael. / Prolonged engraftment of human hepatocytes in mice transgenic for the deleted form of human hepatocyte growth factor. In: Hepatology Research. 2007 ; Vol. 37, No. 10. pp. 854-862.
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