Transplantation · 2003
Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Matsushita Takakazu, Ikai Iwao, Nishitai Ryuta, Katsura Nagato, Yamanokuchi Satoshi, Matsuo Koichi, Sugimoto Shinichi, Shiotani Tomohiro, Takahashi Rei, Terajima Hiroaki, Yamaoka Yoshio
Аннотация
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.
CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.
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.
CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.