Prolonged survival of porcine hepatocytes in cynomolgus monkeys.
OBJECTIVE
Management of patients with liver failure can be a significant medical challenge, and transplantation of the liver is the only definitive therapy. Whole liver allotransplantation is limited by a shortage of human donors and the risks of the surgery in those most ill. Transplants consisting of xenogeneic hepatocytes might overcome these problems, and work in rodents indicates that such transplants can correct some metabolic deficiencies and can prevent the complications and mortality associated with hepatic failure. As a prelude to clinical application, we tested the feasibility of hepatocyte xenotransplantation in nonhuman primates.


METHODS
One to 2 billion hepatocytes from outbred swine were transplanted into the spleens of cynomolgus monkeys using conventional immunosuppression to control rejection. Duration of graft function was determined based on assay for porcine albumin.


RESULTS
Following a single infusion, xenogeneic hepatocytes functioned for more than 80 days and, following re-transplantation, for more than 253 days. Engraftment in the spleen was confirmed 40 days after transplantation by asialoglycoprotein receptor-directed nuclear scanning. The humoral immune response to the transplanted porcine cells had no discernible impact on the survival of the grafts.


CONCLUSIONS
Xenotransplantation of hepatocytes should be explored as a readily available, minimally invasive form of therapy for hepatic failure.
Nagata
Hideo
H
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Nishitai
Ryuta
R
Shirota
Chiyoe
C
Zhang
Jia-Lin
JL
Koch
Cody A
CA
Cai
Jin
J
Awwad
Michel
M
Schuurman
Henk-Jan
HJ
Christians
Uwe
U
Abe
Michio
M
Baranowska-Kortylewicz
Janina
J
Platt
Jeffrey L
JL
Fox
Ira J
IJ
D000818:Animals; D021461:Animals, Outbred Strains; D000910:Antibodies, Heterophile / Q000097:blood; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D017690:Cell Transplantation / Q000379:methods; D005240:Feasibility Studies; D006085:Graft Survival; D022781:Hepatocytes / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D011877:Radionuclide Imaging; D012709:Serum Albumin; D013154:Spleen / Q000000981:diagnostic imaging; D013552:Swine; D013667:Technetium; D014183:Transplantation, Heterologous / Q000379:methods*
D000910:Antibodies, Heterophile; D037263:Asialoglycoprotein Receptor; D007166:Immunosuppressive Agents; D012709:Serum Albumin; D013667:Technetium