Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase).
BACKGROUND
The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human complement regulatory proteins CD55 (hDAF), CD59, and alfa alpha1,2-fucosyltransferase (H-transferase), protected against hyperacute rejection after orthotopic liver xenotransplantation to a baboon and also to study pig liver function in a nonhuman primate.


METHODS
Nine liver transplants from pig to baboon were divided into two groups: a control group (n = 4) of genetically unmodified pigs and an experimental group (n = 5) of pigs transgenic for CD55, CD59, and H-transferase as donors. All the donating piglets obtained through hysterectomy were maintained in specific pathogen-free conditions. The selection of transgenic pig donors followed demonstration of transgene expression using monoclonal antibodies (antiCD55, antiCD59) and immunohistological studies on liver biopsies.


RESULTS
All animals in the control group developed hyperacute rejection with survival rates less than 16 hours without function of transplanted livers. In the experimental group none of the animals suffered hyperacute rejection. Survival in this group was between 13 and 24 hours. The livers were functional, producing bile and maintaining above 35% prothrombin activity. Only in one case was there primary dysfunction of the xenograft.


CONCLUSIONS
Polytransgenic livers for complement regulatory proteins prevent hyperacute rejection when xenotransplanted into a baboon.
Ramírez
P
P
Liver Transplant Unit, Department of Surgery, Virgen Arrixaca University Hospital, Murcia, Spain. ramirezp@um.es
Montoya
M J
MJ
Ríos
A
A
García Palenciano
C
C
Majado
M
M
Chávez
R
R
Muñoz
A
A
Fernández
O M
OM
Sánchez
A
A
Segura
B
B
Sansano
T
T
Acosta
F
F
Robles
R
R
Sánchez
F
F
Fuente
T
T
Cascales
P
P
González
F
F
Ruiz
D
D
Martínez
L
L
Pons
J A
JA
Rodríguez
J I
JI
Yélamos
J
J
Cowan
P
P
d'Apice
A
A
Parrilla
P
P
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000032:analysis / Q000235:genetics; D018957:CD59 Antigens / Q000032:analysis / Q000235:genetics; D005647:Fucosyltransferases / Q000235:genetics; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology*; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D018958:CD55 Antigens; D018957:CD59 Antigens; C502597:FUT7 protein, human; D005647:Fucosyltransferases