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1996 Fiscal Year Final Research Report Summary

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
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
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.

  • Research Products

    (32 results)

All Other

All Publications (32 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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