Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats

Sanjeev Gupta, Pankaj Rajvanshi, Adil N. Irani, Christopher J. Palestro, Kuldeep K. Bhargava

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D- galactosamine (GaIN). Portosystemic shunting was analysed with 99m-Tc- labelled albumin microspheres. GaIN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (> 99% 99m-Tc activity was in the liver in normal and GaIN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GaIN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalJournal of Pathology
Volume190
Issue number2
DOIs
StatePublished - Feb 2000

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Galactosamine
Inbred F344 Rats
Hepatocytes
Cell Proliferation
Liver
Wounds and Injuries
Acute Liver Failure
Cell Transplantation
Technetium Tc 99m Aggregated Albumin
Dipeptidyl Peptidase 4
gamma-Glutamyltransferase
Microspheres
Necrosis
Cell Count
Cell Membrane
Inflammation
DNA
Therapeutics

Keywords

  • Acute liver failure
  • Animal
  • Hepatocyte
  • Toxic
  • Transplantation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats. / Gupta, Sanjeev; Rajvanshi, Pankaj; Irani, Adil N.; Palestro, Christopher J.; Bhargava, Kuldeep K.

In: Journal of Pathology, Vol. 190, No. 2, 02.2000, p. 203-210.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Rajvanshi, Pankaj ; Irani, Adil N. ; Palestro, Christopher J. ; Bhargava, Kuldeep K. / Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats. In: Journal of Pathology. 2000 ; Vol. 190, No. 2. pp. 203-210.
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