Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice

Charles S. Landis, Kosho Yamanouchi, Hongchao Zhou, Sankar Mohan, Namita Roy-Chowdhury, David A. Shafritz, Alan Koretsky, Jayanta Roy-Chowdhury, Hoby P. Hetherington, Chandan Guha

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1250-1258
Number of pages9
JournalHepatology
Volume44
Issue number5
DOIs
StatePublished - Nov 2006

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Hepatocytes
Creatine Kinase
Liver
Transplantation
Cell Proliferation
Hepatocyte Growth Factor
Phosphocreatine
Clinical Protocols
Liver Transplantation
Genes
Liver Diseases
Magnetic Resonance Imaging
Muscles
Brain

ASJC Scopus subject areas

  • Hepatology

Cite this

Landis, C. S., Yamanouchi, K., Zhou, H., Mohan, S., Roy-Chowdhury, N., Shafritz, D. A., ... Guha, C. (2006). Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. Hepatology, 44(5), 1250-1258. https://doi.org/10.1002/hep.21382

Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. / Landis, Charles S.; Yamanouchi, Kosho; Zhou, Hongchao; Mohan, Sankar; Roy-Chowdhury, Namita; Shafritz, David A.; Koretsky, Alan; Roy-Chowdhury, Jayanta; Hetherington, Hoby P.; Guha, Chandan.

In: Hepatology, Vol. 44, No. 5, 11.2006, p. 1250-1258.

Research output: Contribution to journalArticle

Landis, CS, Yamanouchi, K, Zhou, H, Mohan, S, Roy-Chowdhury, N, Shafritz, DA, Koretsky, A, Roy-Chowdhury, J, Hetherington, HP & Guha, C 2006, 'Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice', Hepatology, vol. 44, no. 5, pp. 1250-1258. https://doi.org/10.1002/hep.21382
Landis CS, Yamanouchi K, Zhou H, Mohan S, Roy-Chowdhury N, Shafritz DA et al. Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. Hepatology. 2006 Nov;44(5):1250-1258. https://doi.org/10.1002/hep.21382
Landis, Charles S. ; Yamanouchi, Kosho ; Zhou, Hongchao ; Mohan, Sankar ; Roy-Chowdhury, Namita ; Shafritz, David A. ; Koretsky, Alan ; Roy-Chowdhury, Jayanta ; Hetherington, Hoby P. ; Guha, Chandan. / Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. In: Hepatology. 2006 ; Vol. 44, No. 5. pp. 1250-1258.
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