Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates.
BACKGROUND
We developed an extracorporeal liver perfusion (ECLP) system as a liver-assist device. In this study, we evaluated the safety of the ECLP using human decay accelerating factor (hDAF) transgenic porcine livers in healthy baboons.


METHODS
Livers were isolated from five hDAF transgenic pigs and five nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and healthy baboons were performed without immunosuppressive agents. Cross-circulation was discontinued in any of the following circumstances: elevated hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24-hr well-conditioned cross-circulation.


RESULTS
The cross-circulations with nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three cross-circulations with hDAF transgenic porcine livers were performed for 24 hr; the other two cross-circulations were discontinued at 13 and 17 hr because of massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1 hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver was less than that in the nontransgenic liver, although immunoglobulin-M deposition was comparable. The porcine livers showed no apparent interlobular bleeding or lobular necrosis. All porcine livers maintained bile production during the cross-circulation. No baboons showed any serious complications after the cross-circulation.


CONCLUSIONS
The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.
Matsushita
Takakazu
T
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto, Japan.
Ikai
Iwao
I
Nishitai
Ryuta
R
Katsura
Nagato
N
Yamanokuchi
Satoshi
S
Matsuo
Koichi
K
Sugimoto
Shinichi
S
Shiotani
Tomohiro
T
Takahashi
Rei
R
Terajima
Hiroaki
H
Yamaoka
Yoshio
Y
D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000032:analysis; D018958:CD55 Antigens / Q000235:genetics*; D003167:Complement Activation / Q000276:immunology*; D005112:Extracorporeal Circulation / Q000379:methods*; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000601:surgery; D008102:Liver Circulation; D017114:Liver Failure, Acute / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D016031:Liver Transplantation; D010215:Papio; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014019:Tissue Donors
D000910:Antibodies, Heterophile; D018958:CD55 Antigens