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 journalArticle

34 Citations (Scopus)

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
StatePublished - 2001

Fingerprint

Liver
Amplification
Hepatocytes
Tissue Donors
Artificial Liver
Gene transfer
Gene therapy
Alkaloids
Metabolic Diseases
Homologous Transplantation
Hepatectomy
Cell death
Liver Neoplasms
Reperfusion Injury
Thyroid Hormones
Mitosis
Genetic Therapy
Transgenic Mice
Growth Hormone
Intercellular Signaling Peptides and Proteins

Keywords

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

ASJC Scopus subject areas

  • Biophysics

Cite this

Guha, C., Deb, N. J., Sappal, B. S., Ghosh, S. S., Roy-Chowdhury, N., & Roy-Chowdhury, J. (2001). Amplification of engrafted hepatocytes by preparative manipulation of the host liver. Artificial Organs, 25(7), 522-528.

Amplification of engrafted hepatocytes by preparative manipulation of the host liver. / Guha, Chandan; Deb, Niloy J.; Sappal, Baljit S.; Ghosh, Siddhartha S.; Roy-Chowdhury, Namita; Roy-Chowdhury, Jayanta.

In: Artificial Organs, Vol. 25, No. 7, 2001, p. 522-528.

Research output: Contribution to journalArticle

Guha, C, Deb, NJ, Sappal, BS, Ghosh, SS, Roy-Chowdhury, N & Roy-Chowdhury, J 2001, 'Amplification of engrafted hepatocytes by preparative manipulation of the host liver', Artificial Organs, vol. 25, no. 7, pp. 522-528.
Guha, Chandan ; Deb, Niloy J. ; Sappal, Baljit S. ; Ghosh, Siddhartha S. ; Roy-Chowdhury, Namita ; Roy-Chowdhury, Jayanta. / Amplification of engrafted hepatocytes by preparative manipulation of the host liver. In: Artificial Organs. 2001 ; Vol. 25, No. 7. pp. 522-528.
@article{e660d1c5131747e8817e7d63305ee643,
title = "Amplification of engrafted hepatocytes by preparative manipulation of the host liver",
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.",
keywords = "Hepatocyte transplantation, Liver malignancies, Liver-directed gene therapy, Preparative irradiation, Radiation-induced liver damage",
author = "Chandan Guha and Deb, {Niloy J.} and Sappal, {Baljit S.} and Ghosh, {Siddhartha S.} and Namita Roy-Chowdhury and Jayanta Roy-Chowdhury",
year = "2001",
language = "English (US)",
volume = "25",
pages = "522--528",
journal = "Artificial Organs",
issn = "0160-564X",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Amplification of engrafted hepatocytes by preparative manipulation of the host liver

AU - Guha, Chandan

AU - Deb, Niloy J.

AU - Sappal, Baljit S.

AU - Ghosh, Siddhartha S.

AU - Roy-Chowdhury, Namita

AU - Roy-Chowdhury, Jayanta

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Hepatocyte transplantation

KW - Liver malignancies

KW - Liver-directed gene therapy

KW - Preparative irradiation

KW - Radiation-induced liver damage

UR - http://www.scopus.com/inward/record.url?scp=0035406246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035406246&partnerID=8YFLogxK

M3 - Article

VL - 25

SP - 522

EP - 528

JO - Artificial Organs

JF - Artificial Organs

SN - 0160-564X

IS - 7

ER -