Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver.
Cell transplantation into hepatic sinusoids, which is necessary for liver repopulation, could cause hepatic ischemia. To examine the effects of cell transplantation on host hepatocytes, we transplanted Fisher 344 rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. Within 24 h of cell transplantation, areas of ischemic necrosis, along with transient disruption of gap junctions, appeared in the liver. Moreover, host hepatocytes expressed gamma-glutamyl transpeptidase (GGT) extensively, which was observed even 2 years after cell transplantation. GGT expression was not associated with alpha-fetoprotein activation, which is present in progenitor cells. Increased GGT expression was apparent after transplantation of nonparenchymal cells and latex beads but not after injection of saline, fragmented hepatocytes, hepatocyte growth factor, or turpentine. Some host hepatocytes exhibited apoptosis, as well as DNA synthesis, between 24 and 48 h after cell transplantation. Changes in gap junctions, GGT expression, DNA synthesis, and apoptosis after cell transplantation were prevented by vasodilators. The findings indicated the onset of ischemic liver injury after cell transplantation. These hepatic perturbations must be considered when transplanted cells are utilized as reporters for biological studies.
Gupta
S
S
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA. sanjvgupta@pol.net
Rajvanshi
P
P
Malhi
H
H
Slehria
S
S
Sokhi
R P
RP
Vasa
S R
SR
Dabeva
M
M
Shafritz
D A
DA
Kerr
D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D017629:Gap Junctions / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000166:cytology*; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014184:Transplantation, Homologous / Q000502:physiology*; D005723:gamma-Glutamyltransferase / Q000235:genetics*
D005723:gamma-Glutamyltransferase