Project/Area Number |
07507003
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 試験 |
Research Field |
Digestive surgery
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
YAMAOKA Yosio Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90089102)
|
Co-Investigator(Kenkyū-buntansha) |
MORI Naoki IHARA ELECTRONICS Co., Inc.Research worker, 開発室, 研究員
TAKENAKA Yoshinori ASAHI MEDICAL Co., Inc.Research worker, 技術第一部, 研究員
OZAKI Nobuhiro Kyoto University, Graduate School of Medicine, Intructor, 医学研究科, 助手 (50211818)
INAMOTO Takashi Kyoto University, College of Medical Technology, Professor, 医療短期大学部, 教授 (10135577)
IKAI Iwao Kyoto University, Graduate School of Medicine, Intructor, 医学研究科, 助手 (60263084)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥36,200,000 (Direct Cost: ¥36,200,000)
Fiscal Year 1996: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1995: ¥25,200,000 (Direct Cost: ¥25,200,000)
|
Keywords | Liver Fallure / Liver Xenoperfusion / Liver Assist Device / Humoral Injury / Prostaglandin E1 / Soluble Complement Receptor Type 1 (sCR1) / プロスタグランジンE1 / 人工肝補助装置 / 体外肝灌流 / 超急性拒絶反応 / 1型可溶性補体受容体 / 異種血液灌流 / 常温持続灌流 / 可溶性補体受容体 |
Research Abstract |
To assist various functions of the liver, usage of the xenogeneic pig liver as a liver assist device were evaluated in this progect. In this study, our original liver perfusion system, including continuous prostaglandin E1 administration, short cold ischemic time, physiological conditioning, enabled the pig liver to be xenoperfused more than 9 hours with adequate hepatic metabolic capacity. With this system, we succeeded in effective liver assist of the surgically induced liver failure dogs. These results were presented at both congresses of the American Society of the Artificial Internal Organ and American Society of Transplantation Physician in 1997. However, long-term pig liver xenoperfusion causes severe humoral injury via activation of human complement system by human anti-porcine xenoantigen. Hence, we had to conquer this xenogeneic humoral injury to develop more potent liver assist device. In this study, we revealed that recombinant soluble Complement Receptor type I (sCR1) dramatically suppressed humoral injury during xenoperfusion of the pig liver with human whole blood. With sCR1, xenoperfusion of the pig whole liver could be continued more than 24 hours with high hepatic function. To introduce this system to the clinical field, we established the xenogeneic organ usage system in April 1997 in Kyoto University Hospital. Now, we are evaluating the safety of the pig liver xenoperfusion system with baboon instead of human as a preclinical study.
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