Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice.
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.
Landis
Charles S
CS
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Yamanouchi
Kosho
K
Zhou
Hongchao
H
Mohan
Sankar
S
Roy-Chowdhury
Namita
N
Shafritz
David A
DA
Koretsky
Alan
A
Roy-Chowdhury
Jayanta
J
Hetherington
Hoby P
HP
Guha
Chandan
C
D000818:Animals; D002455:Cell Division; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage; D022781:Hepatocytes / Q000201:enzymology / Q000528:radiation effects / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism* / Q000528:radiation effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D011829:Radiation Dosage; D012044:Regression Analysis; D019076:Transgenes / Q000502:physiology; D019172:Transplantation Conditioning
D010725:Phosphocreatine; D010758:Phosphorus; D017228:Hepatocyte Growth Factor; D003402:Creatine Kinase