Hepatic function after genetically engineered pig liver transplantation in baboons.
BACKGROUND
If "bridging" to allo-transplantation (Tx) is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured.


METHODS
We have studied hepatic function in baboons after Tx of livers from alpha1,3-galactosyltransferase gene-knockout (GTKO, n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46, n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In four baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs.


RESULTS
Recipient baboons died or were euthanized after 4 to 7 days after internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, and plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed.


CONCLUSIONS
After the Tx of genetically engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near normal; (2) there was evidence for production of pig proteins, including coagulation factors; and (3) these appeared to function adequately in baboons although interspecies compatibility of such proteins remains to be confirmed.
Ekser
Burcin
B
Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Echeverri
Gabriel J
GJ
Hassett
Andrea Cortese
AC
Yazer
Mark H
MH
Long
Cassandra
C
Meyer
Michael
M
Ezzelarab
Mohamed
M
Lin
Chih Che
CC
Hara
Hidetaka
H
van der Windt
Dirk J
DJ
Dons
Eefje M
EM
Phelps
Carol
C
Ayares
David
D
Cooper
David K C
DK
Gridelli
Bruno
B
D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D010215:Papio; D011516:Prothrombin / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D016559:Tacrolimus / Q000627:therapeutic use; D014183:Transplantation, Heterologous / Q000276:immunology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000502:physiology
D001779:Blood Coagulation Factors; D007166:Immunosuppressive Agents; D011516:Prothrombin; D016559:Tacrolimus