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Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31 P MRS imaging in mice
Author(s) -
Landis Charles S.,
Yamanouchi Kosho,
Zhou Hongchao,
Mohan Sankar,
RoyChowdhury Namita,
Shafritz David A.,
Koretsky Alan,
RoyChowdhury Jayanta,
Hetherington Hoby P.,
Guha Chandan
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21382
Subject(s) - hepatocyte , liver transplantation , transplantation , hepatocyte growth factor , liver regeneration , cancer research , biology , creatine kinase , phosphocreatine , pathology , medicine , regeneration (biology) , microbiology and biotechnology , endocrinology , biochemistry , receptor , in vitro , energy metabolism
Hepatocyte transplantation (HT) is being explored as a substitute for liver transplantation for the treatment of liver diseases. For the clinical application of HT, a preparative regimen that allows preferential proliferation of transplanted cells in the host liver and a noninvasive method to monitor donor cell engraftment, proliferation, and immune rejection would be useful. We describe an imaging method that employs the creatine kinase (CK) gene as a marker of donor hepatocytes. Creatine kinase is unique among marker genes, because it is normally expressed in brain and muscle tissues and is therefore not immunogenic. Preferential proliferation of transplanted CK‐expressing hepatocytes was induced by preparative hepatic irradiation and expression of hepatocyte growth factor using a recombinant adenoviral vector. CK is normally not expressed in mouse liver and its expression by the donor cells led to the production of phosphocreatine in the host liver, permitting 31 P magnetic resonance spectroscopic imaging of liver repopulation by engrafted hepatocytes. In conclusion , this study combined a noninvasive imaging technique to assess donor hepatocyte proliferation with a preparative regimen of partial liver irradiation that allowed regional repopulation of the host liver. Our results provide groundwork for future development of clinical protocols for HT. (H EPATOLOGY 2006;44:1250–1258.)