Hepatocyte transplantation in a model of toxin-induced liver disease: variable therapeutic effect during replacement of damaged parenchyma by donor cells.
To provide long-term therapy in patients with severe toxin-induced hepatic parenchymal damage, donor hepatocytes would need to replicate and replace a large portion of the damaged parenchyma. Using a mouse model developed to reproduce this type of hepatic injury, we found that hepatocyte transplantation only slightly improved survival after transplantation despite the fact that many non-survivors showed moderate liver repopulation by donor cells. Perhaps accounting for this outcome, donor parenchyma in non-survivors did not have typical lobular organization. These results indicate that the re-creation of functional parenchyma by transplanted hepatocytes requires time, during which donor cells proliferate and then establish normal parenchymal architecture.
Braun
K M
KM
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Degen
J L
JL
Sandgren
E P
EP
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D017690:Cell Transplantation; D018572:Disease-Free Survival; D004742:Enhancer Elements, Genetic; D015774:Ganciclovir / Q000633:toxicity*; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012709:Serum Albumin / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics
D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D008668:Metallothionein; D013937:Thymidine Kinase; D000469:Alkaline Phosphatase; D015774:Ganciclovir