Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation.
Transplantation of xenogeneic hepatocytes would provide a novel therapy for liver disease and would help to solve the problem of an insufficient supply of donor organs. We have tested whether xenogeneic cells infused into the liver could correct the metabolic defect in the Watanable heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous familial hypercholesterolemia, and we have investigated whether the infused cells traverse the lining of the portal vasculature. We find that porcine hepatocytes are localized in the hepatic sinusoids after surgery and subsequently migrate out of the vessels and integrate into the hepatic parenchyma. The integrated porcine hepatocytes provide functional LDL receptors that lower serum cholesterol in the WHHL rabbit by 30-60% for at least 100 days.
Gunsalus
J R
JR
Department of Molecular and Cellular Biology, Diacrin Inc., Charlestown, Massachusetts 02129, USA.
Brady
D A
DA
Coulter
S M
SM
Gray
B M
BM
Edge
A S
AS
D000818:Animals; D017690:Cell Transplantation; D002784:Cholesterol / Q000097:blood*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000628:therapy; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D011817:Rabbits; D013552:Swine; D013997:Time Factors; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D008077:Lipoproteins, LDL; D002784:Cholesterol