• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of the artificial liver assist device with normothermic xenoperfusion system of the whole liver

Research Project

Project/Area Number 07507003
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Digestive surgery
Research InstitutionKYOTO 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)
KeywordsLiver 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.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] H. Terajima: "Timing of transplantation and donor selection in living related liver transplantation for fulminant wilson′s disease." Transplantation Proceedings. 27. 1177-1178 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y. Shirakawa: "Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506." Transplantation. 60. 1582-1587 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Shinohara: "Direct measurement of hepatic indocyanine green clearance with near-infrared spectroscopy : Separate evalution of uptake and removal." Hepatology. 23. 137-144 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Terajima: "Assessment of hyaluronate clearance and endothelin production during extracorporeal xenogeneic pig liver perfusion." Transplantation Proceedings.28. 633-634 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S. Satoh: "Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy." Gastroenterology. 110. 1166-1174 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Yagi: "Discordant effects of xenogenic pig liver perfusion on function of sinusoidal endothelial cells and parenchymal cells." Transprantation Proceedings. 28. 1402-1403 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Terajima: "Long-duration xenogeneic extracorporeal pig liver perfusion with human blood." Transpl. Int.9. S388-S391 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Terajima: "Successful long-term xenoperfusion of the pig liver :" Transplantation. 63. 507-512 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Shinohara: "Prostaglandin E1 resuscitates hepatic organic anion transport independent of its hemodynamic effect after warm ischemia" Journal of Surgical Research. 68. 56-62 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N. Shinkura: "Presence of anti-FKBP12 autoantibodies in patients with liver allografts" Transplantation. 64. 1336-1342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Yagi: "The protective effects of prostaglandin E_1 on sinusoidal endothelial cells in xenogeneic pig liver perfusion" Journal of surgical research. 73. 28-34 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Yagi: "Extracorporeal xenoperfusion of the pig liver as a liver assist device : Effects of prostaglandin E_1 and soluble complement receptor type 1" Transplantation Proceedings. 30. 74-75 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. Kanazawa: "Soluble complement receptor Type 1 (sCR1) suppresses the sinusoidal endothelial cell (SEC) activation in the xenoperfused liver." Hepatology. 24. 431A (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S. Satoh: "Humoral injury in porcine livers perfused with human whole blood." Transplantation. 64. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. Kanazawa: "Effect of soluble complement receptor (sCR1) on activation of the sinusoidal endothelial cell (SEC) and Kupffer call in the xenoperfused pig liver." Hepatology. 26. 534A (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. Kanazawa: "Suppression of endotoxin-induced ICAM-1 Expression and liver damage in the transgenic mouse liver expressing creatine kinase." Hepatology. 26. 189A (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terajima: "Timing of transplantation and donor selection in living related liver transplantation for fulminant wilson's disease." Transplantation Proceedings. 27 (1). 1177-1178 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Shirakata: "Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506." Transplantation. 60 (12). 1582-1587 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Shinohara: "Direct measurement of hepatic indocyanine green clearance with near-infrared spectroscopy : Separate evalution of uptake and removal." Hepatology. 23 (1). 137-144 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terajima: "Assessment of hyaluronate clearance and endothelin production during extracorporeal xenogeneic pig liver perfusion." Transplantaion Proceedings. 28 (2). 633-634 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Satoh: "Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy." Gastroenterology. 110. 1166-1174 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Yagi: "Discordant effects of xenogeneic pig liver perfusion on function of sinusoidal endothelial cells and parenchymal cells." Transprantation Proceedings. 28 (3). 1402-1403 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terajima: "Long-duration xenogeneic extracorporeal pig liver perfusion with human blood." Transpl.Int.9. S388-S391 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terajima: "Successful long-term xenoperfusion of the pig liver" Transplantation. 63 (4). 507-512 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Shinohara: "Prostaglandin E1 resuscitates hepatic organic anion transport independent of its hemodynamic effect after warm ischemia" Journal of Surgical Research. 68. 56-62 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Shinkura: "Presence of anti-FKBP12 autoantibodies in patients with liver allografts" Transplantation. 64 (9). 1336-1342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Yagi: "The protective effects of prostaglandin E,on sinusoidal endothelial cells in xenogeneic pig liver perfusion" Journal of surgical research. 73 (1). 28-34 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Yagi: "Extracorporeal xenoperfusion of the pig liver as a liver assist device : Effects of prostaglandin E,and soluble complement receptor type 1" Transplantation Proceedings. 30. 74-75 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Kanazawa: "Soluble complement receptor Type 1 (sCR1) suppresses the sinusoidal endothelial cell (SEC) activation in the xenoperfused liver." Hepatology. 24 (4) Pt.2. 431A (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Satoh: "Humoral injury in porcine livers perfused with human whole blood." Transplantation. 64 (8) (in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Kanazawa: "Effect of soluble complement receptor type I (sCR1) on activation of the sinusoidal endothelial cell (SEC) and Kupffer cell in the xenoperfused pig liver." Hepatology AASLD abstract. 534A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Kanazawa: "Suppression of endotoxin-induced ICAM-1 Expression and liver damage in the transgenic mouse liver expressing creatine kinase." Hepatology. 26 (4) Pt.2 AASLD abstracts. 189A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroaki Terajima: "Successful long-term xenoperfusion of the pig liver : continuous administration of prostaglandin E1 and insulin." Transplantation. in press

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroaki Terajima: "Long-duration xenogeneic extracorporeal pig liver perfusion with human whole blood." Transplant International. 9 Suppl.1. S388-S391 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroaki Terajima: "Assessment of hyaluronate clearance and endothelin production during extracorporeal xenogeneic pig liver perfusion." Transplantation Proceedings. 28. 633-634 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toshikazu Yagi: "Discordant effects of xenogeneic pig liver perfusion on function of sinusoidal endothelial cells and parenchymal cells." Transplantation Proceedings. 28. 1402-1403 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐藤誠二: "ブタ肝を用いた異種体外肝灌流による肝補助装置の開発" 外科治療. 75(6). 722-723 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroaki Terajima: "The effects of soluble complement receptor type 1 on hyperacute rejection in ex vivo xenoperfusion of the porcine liver." European Surgical Research. (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroaki Terajima: "Newly developed xenogeneic pig liver perfusion system for utilization as an extracorporeal liver assist device." European Surgical Research. 27(S1). 51-51 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] HIROAKI TERAJIMA: "Long-duration xenogeneic extracorporeal pig liver perfusion with human blood" Transplant International. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] HIROAKI TERAJIMA: "Assessment of hyaluronate clearance and endothelin production during extracorporeal xenogeneic pig liver perfusion" Transplantation Proceedings. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] HIROAKI TERAJIMA: "Newly developed xenogeneic pig liver perfusion system for utilization as an extracorporeal liver assist device" European Surgical Research. 27(S1). 51-51 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] HIROAKI TERAJIMA: "The effects of soluble complement receptor type 1 on hyperacute rejection in ex vivo xenoperfusion of the porcine liver" European Surgical Research. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] TOSHIKAZU YAGI: "Discordant effect of xenogeneic pig liver perfusion on functions of sinusoidal endothelial cells and parenchymal cells" TranspIantation Proceedings. (in press). (1996)

    • Related Report
      1995 Annual Research Report

URL: 

Published: 1995-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi