Liver irradiation: A potential preparative regimen for hepatocyte transplantation

Chandan Guha, Bhupesh Parashar, Niloy J. Deb, Anand Sharma, Giridhar R. Gorla, Alan Alfieri, Namita Roy-Chowdhury, Jayanta Roy-Chowdhury, Bhadrasain Vikram

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Advances in the understanding of hepatocyte engraftment and repopulation of the host liver have already led to the use of hepatocyte transplantation (HT) with some success in the treatment of inherited and acquired liver diseases. Wider application of HT is severely limited by the unavailability of large number of transplantable hepatocytes and difficulties associated with transplanting an adequate number of cells for achieving therapeutically satisfactory levels of metabolic correction. Therefore, there is a need for preparative regimens that provide a growth advantage to the transplanted (healthy) hepatocytes over the host's own (diseased) hepatocytes so that the former can repopulate the host liver. We have recently shown that when the liver of recipient rats was subjected to radiotherapy and partial hepatectomy before HT, the transplanted hepatocytes engrafted in and massively repopulated the liver, and also ameliorated the adverse clinical and histopathological changes associated with hepatic irradiation. This protocol was then used as a preparative regimen for transplanting normal hepatocytes into jaundice mutant rats (Gunn strain), which lack hepatic bilirubin-uridinediphosphoglucuronate glucuronosyltransferase and is a model of Crigler-Najjar syndrome Type I. The results showed long-term correction of the metabolic abnormality, suggesting that the transplanted hepatocytes repopulated an irradiated liver and were metabolically functional. This strategy could be useful in the treatment of various genetic, metabolic, or malignant diseases of the liver.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume49
Issue number2
DOIs
StatePublished - Feb 1 2001

Keywords

  • Hepatocyte transplantation
  • Liver malignancies
  • Radiation therapy
  • Radiation-induced liver damage

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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