Life supporting function for over one month of a transgenic porcine heart in a baboon.
BACKGROUND
Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression.


METHODS
Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy.


RESULTS
The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection.


CONCLUSIONS
This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.
Vial
C M
CM
Department of Surgery, Stanford University School of Medicine, CA, USA.
Ostlie
D J
DJ
Bhatti
F N
FN
Cozzi
E
E
Goddard
M
M
Chavez
G P
GP
Wallwork
J
J
White
D J
DJ
Dunning
J J
JJ
D000818:Animals; D030801:Animals, Genetically Modified; D000917:Antibody Formation; D018958:CD55 Antigens; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008020:Life Support Care; D009206:Myocardium / Q000473:pathology; D010215:Papio; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous
D018958:CD55 Antigens; D007166:Immunosuppressive Agents