TY - JOUR
T1 - Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice
AU - Landis, Charles S.
AU - Yamanouchi, Kosho
AU - Zhou, Hongchao
AU - Mohan, Sankar
AU - Roy-Chowdhury, Namita
AU - Shafritz, David A.
AU - Koretsky, Alan
AU - Roy-Chowdhury, Jayanta
AU - Hetherington, Hoby P.
AU - Guha, Chandan
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11
Y1 - 2006/11
N2 - 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 31P 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.
AB - 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 31P 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.
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U2 - 10.1002/hep.21382
DO - 10.1002/hep.21382
M3 - Article
C2 - 17058269
AN - SCOPUS:33751010492
SN - 0270-9139
VL - 44
SP - 1250
EP - 1258
JO - Hepatology
JF - Hepatology
IS - 5
ER -