Amplification of engrafted hepatocytes by preparative manipulation of the host liver

Chandan Guha, Niloy J. Deb, Baljit S. Sappal, Siddhartha S. Ghosh, Namita Roy-Chowdhury, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Scarcity of donor livers is a major obstacle to the general application of hepatocytes for the development of bioartificial liver assist devices as well as intracorporeal engraftment of hepatocytes for the treatment of inherited metabolic diseases. The number of hepatocytes that can be transplanted into the liver safely in a single sitting also limits the utility of this procedure. These limitations could be addressed by providing preferential proliferative advantage to the transplanted cells. Studies using transgenic mouse recipients or donors have indicated that massive repopulation of the host liver by engrafted hepatocytes requires that the transplanted cells are subjected to a proliferative stimulus to which the host hepatocytes cannot respond. Prevention of host hepatocyte proliferation has been achieved by treatment with a plant alkaloid, retrorsine. Because retrorsine is carcinogenic, we have evaluated preparative irradiation for this purpose. The proliferative stimulus may consist of the loss of hepatic mass (e.g., partial hepatectomy, reperfusion injury or induction of Fas-mediated apoptosis by gene transfer) or administration of stimulants of hepatocellular mitosis (e.g., growth factors or thyroid hormone). Potential applications of these preparative manipulations of the host liver include the treatment of inherited metabolic disorders by transplantation of allogeneic hepatocytes, hepatocyte-mediated ex vivo gene therapy, rescuing liver cancer patients from radiation-induced liver damage, and expansion of human hepatocytes in animal livers.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalArtificial Organs
Volume25
Issue number7
DOIs
StatePublished - Jan 1 2001

Keywords

  • Hepatocyte transplantation
  • Liver malignancies
  • Liver-directed gene therapy
  • Preparative irradiation
  • Radiation-induced liver damage

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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