1997 年度実績報告書

同種移植及び異種移植における遺伝子制御の研究

研究課題

研究課題/領域番号	09307023
研究種目	基盤研究(A)
研究機関	名古屋大学
研究代表者	林衆治名古屋大学, 医学部, 助手 (30218573)
研究分担者	鬼頭純三名古屋大学, 医学部, 教授 (60022802) 高木弘名古屋大学, 医学部, 教授 (70154755) 横山逸男名古屋大学, 医学部, 講師 (60240206)
キーワード	gene therapy / transplantation / adenovirol vector / immunosuppression / rejection / preservation / shock / gene trageting
研究概要	臓器移植は、免疫抑制療法の進歩及び臓器保存法の発展により現在では確立された治療手段となっている。最近臓器提供者(ドナー)不足という問題がクローズアップされてきており、欧米では深刻な社会的問題となりつつある。このドナー不足を解決する手段として、動物の臓器を用いるいわゆる異種移植の必要性が近年世界中で提唱されるようになってきている。しかし、異種移植では同種移植に比較してはるかに免疫学的障害が大きく、従来の免疫抑制療法では臨床応用は不可能と考えられている。また、同種移植は、すでに一般的な治療手段として確立されているが、臓器保存時間の限界、免疫抑制剤の服用など移植患者のquality of lifeとも関係する多くの問題を有している。従来の免疫抑制療法、従来の臓器保存法の限界をブレークスルーする手法として、我々は、分子生物学的手法特に近年欧米および日本で臨床応用されつつある遺伝子治療の技術に注目して以下に項目につき、研究成果を得た。 1)CTLA4Ig遺伝子導入により、ラット同種心臓移植モデルでは、免疫抑制剤を用いずに拒絶反応抑制可能であること、また、免疫抑制剤であるFK506との併用により相乗効果が認められること、2)Ikβ遺伝子導入により虚血再環流障害が抑制されること、3)interleukin 10(IL10)遺伝子導入により、腹膜炎ショックモデルで治療効果を認めること、4)tissue plsminogen activator(tPA)遺伝子及びIL10遺伝子により、delayed graft rejectionが治療可能であること、の研究成果を得た。アデノウイルスベクターにおけるノブ改変ベクターとして、ファイバーノブ先端にリジン20残基を組み込んだ新しいアデノウイルスベクターを作成したが、高力価を得ることができなかった。今後の検討課題である。

研究成果

(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] S Hayashi,H Takagi: "Adenovirus-mediated gene transfer to the xenogeneic in liver xenotransplantation : The transduction of complement regulatory factor genes (DAF and HRF20)" Transplantation Proceeding. 29. 2211-2211 (1997)
[文献書誌] S Hayashi,H Takagi: "Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell transplantation" Transplantation Proceeding. 29. 2212-2212 (1997)
[文献書誌] S Hayashi,H Takagi: "Adenovirus-mediated gene transfer of anitisense ribozyme for α (1,3) garactosyl transferase gene and (1,2) fucosyl transferase gene in xenotranplantation" Transplantation Proceeding. 29. 2213-2213 (1997)
[文献書誌] Y Namii,S Hayashi,H Takagi: "Evidence that the adenoviral vector containing the CTLA-Ig gene improves transgene expression and graft survival" Transplantation Proceeding. 29. 1738-1739 (1997)
[文献書誌] H Asano,S Hayashi,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation" Tissue Antigenes,in press. 50. 484-488 (1997)
[文献書誌] 林衆治,高木弘: "特集寛容導入をめざす移植免疫学-ヒト遺伝子導入による異種拒絶反応制御" Molecular Medicin. 34-7. (1997)
[文献書誌] 白倉良太,林衆治: "臓器移植と分子生物学-移植成績向上に向けた遺伝子操作の現状と課題" TREANDS & TOPICS IN TRANSPLANTATION. 8-1. 18-26 (1997)
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Apoptosis in pig endothelial cells after reperfusion and its prevention genetic induction of human Cu,Zn-SOD cDNA" Transplant Proc. 29. 1364-1364 (1997)
[文献書誌] Hayashi S,Takagi H: "Effect of antisense ribozyme to alpha (1,3) galactosyl transferase gene on the expression of GAl alpha (1,3) GAL epitope" Transplant Proc. 29. 893-893 (1997)
[文献書誌] Koike C,Hayashi S,Takagi H: "Reduction of α-gal epitopes in transgenic pig by introduction of human α 1-2 fucosyltransferase." Transplant Proc. 29. 894-894 (1997)
[文献書誌] Negita K,Hayashi S,Takagi H: "Protective effect of human suoeroxide dismutase cDNA transfection in the prevention of cold preservation injury." Transplant Proc. 29. 1363-1363 (1997)
[文献書誌] T Nagasaka,S Hayashi,H Takagi: "α-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation." BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMUNICATIONS. 232. 731-736 (1997)
[文献書誌] Negita M,Hayashi S,Takagi H: "Protective Effect of Human Superoxide Dismutase cDNA Transfection in the Prevention of Cold Preservation Injury" Transplantation Proceedings. 29. 1363-1363 (1997)
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Apoptosis inpig Endothelial Cells After Reperfusion and Its Prevention by Induction of Human Cu,Zn-SOD cDNA" Transplantation Proceedings. 29. 1364-1364 (1997)
[文献書誌] Hayashi S,Takagi H: "Effect of CTL4-Ig Gene Transfer Using Adenoviral Vector in Organ and Cell transplantation" Transplantation Proceedings. 29. 2212-2212 (1997)
[文献書誌] Katayama A,Hayashi S,Takagi H: "Studies of α-Gal Dependent Hyperacute Xenotransplant Rejection Using DOuble Knockout Embryonic Stem Cells." Transplantation Proceedings. 129. 751-756 (1997)
[文献書誌] Shuji Hayashi: "Xenotransplantation with Special Reference to Genetic Engineering" Microbiolm Immunol. 41-10. 751-756 (1997)
[文献書誌] H Asano,S Hayashi,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation" TISSUE ANTIGENS. 50. 484-488 (1997)
[文献書誌] S Hayashi,N Emi,I Yokomaya,Y Namii,k Uchida,and H Takagi: "Inhibition of establishment of Hepatic metastasis in mice by combination gene therapy using both herpes simplex virusthymidine kinase and granulocyte macrophage-colony stimulating factor gene in mune colon cancer" Cancer Gene Therapy. 4-6. 339-344 (1997)
[文献書誌] T Kojima,S Hayashi,H Takagi: "Inhibition of completment-mediated immune hemolysis by the constant domain of immunoglobuin" Peptido Chemistry (in press).
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Transplant Portal venous flow velocity measured by the implantable miniature Doppler probe in pig liver transplantation." International (in press).
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Fas antigen expression and its modification by immunosuppressants." Dig Dis Sci (in press).
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Prevention of endothelial cell apoptosis with genetic induction of human Cu,Zn-SOD cDNA." Transplantation (in press).
[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Portal venous flow velocity measured by the implantable miniature Doppler probe in pig liver transplantation International" (in press).

1997 年度 実績報告書

同種移植及び異種移植における遺伝子制御の研究

研究代表者

林 衆治 名古屋大学, 医学部, 助手 (30218573)

研究成果

[文献書誌] S Hayashi,H Takagi: "Adenovirus-mediated gene transfer to the xenogeneic in liver xenotransplantation : The transduction of complement regulatory factor genes (DAF and HRF20)" Transplantation Proceeding. 29. 2211-2211 (1997)

[文献書誌] S Hayashi,H Takagi: "Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell transplantation" Transplantation Proceeding. 29. 2212-2212 (1997)

[文献書誌] S Hayashi,H Takagi: "Adenovirus-mediated gene transfer of anitisense ribozyme for α (1,3) garactosyl transferase gene and (1,2) fucosyl transferase gene in xenotranplantation" Transplantation Proceeding. 29. 2213-2213 (1997)

[文献書誌] Y Namii,S Hayashi,H Takagi: "Evidence that the adenoviral vector containing the CTLA-Ig gene improves transgene expression and graft survival" Transplantation Proceeding. 29. 1738-1739 (1997)

[文献書誌] H Asano,S Hayashi,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation" Tissue Antigenes,in press. 50. 484-488 (1997)

[文献書誌] 林 衆治,高木 弘: "特集 寛容導入をめざす移植免疫学-ヒト遺伝子導入による異種拒絶反応制御" Molecular Medicin. 34-7. (1997)

[文献書誌] 白倉良太,林 衆治: "臓器移植と分子生物学-移植成績向上に向けた遺伝子操作の現状と課題" TREANDS & TOPICS IN TRANSPLANTATION. 8-1. 18-26 (1997)

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Apoptosis in pig endothelial cells after reperfusion and its prevention genetic induction of human Cu,Zn-SOD cDNA" Transplant Proc. 29. 1364-1364 (1997)

[文献書誌] Hayashi S,Takagi H: "Effect of antisense ribozyme to alpha (1,3) galactosyl transferase gene on the expression of GAl alpha (1,3) GAL epitope" Transplant Proc. 29. 893-893 (1997)

[文献書誌] Koike C,Hayashi S,Takagi H: "Reduction of α-gal epitopes in transgenic pig by introduction of human α 1-2 fucosyltransferase." Transplant Proc. 29. 894-894 (1997)

[文献書誌] Negita K,Hayashi S,Takagi H: "Protective effect of human suoeroxide dismutase cDNA transfection in the prevention of cold preservation injury." Transplant Proc. 29. 1363-1363 (1997)

[文献書誌] T Nagasaka,S Hayashi,H Takagi: "α-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation." BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMUNICATIONS. 232. 731-736 (1997)

[文献書誌] Negita M,Hayashi S,Takagi H: "Protective Effect of Human Superoxide Dismutase cDNA Transfection in the Prevention of Cold Preservation Injury" Transplantation Proceedings. 29. 1363-1363 (1997)

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Apoptosis inpig Endothelial Cells After Reperfusion and Its Prevention by Induction of Human Cu,Zn-SOD cDNA" Transplantation Proceedings. 29. 1364-1364 (1997)

[文献書誌] Hayashi S,Takagi H: "Effect of CTL4-Ig Gene Transfer Using Adenoviral Vector in Organ and Cell transplantation" Transplantation Proceedings. 29. 2212-2212 (1997)

[文献書誌] Katayama A,Hayashi S,Takagi H: "Studies of α-Gal Dependent Hyperacute Xenotransplant Rejection Using DOuble Knockout Embryonic Stem Cells." Transplantation Proceedings. 129. 751-756 (1997)

[文献書誌] Shuji Hayashi: "Xenotransplantation with Special Reference to Genetic Engineering" Microbiolm Immunol. 41-10. 751-756 (1997)

[文献書誌] H Asano,S Hayashi,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation" TISSUE ANTIGENS. 50. 484-488 (1997)

[文献書誌] T Kojima,S Hayashi,H Takagi: "Inhibition of completment-mediated immune hemolysis by the constant domain of immunoglobuin" Peptido Chemistry (in press).

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Transplant Portal venous flow velocity measured by the implantable miniature Doppler probe in pig liver transplantation." International (in press).

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Fas antigen expression and its modification by immunosuppressants." Dig Dis Sci (in press).

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Prevention of endothelial cell apoptosis with genetic induction of human Cu,Zn-SOD cDNA." Transplantation (in press).

[文献書誌] Yokoyama I,Hayashi S,Takagi H: "Portal venous flow velocity measured by the implantable miniature Doppler probe in pig liver transplantation International" (in press).

1997 年度実績報告書

林衆治名古屋大学, 医学部, 助手 (30218573)

[文献書誌] 林衆治,高木弘: "特集寛容導入をめざす移植免疫学-ヒト遺伝子導入による異種拒絶反応制御" Molecular Medicin. 34-7. (1997)

[文献書誌] 白倉良太,林衆治: "臓器移植と分子生物学-移植成績向上に向けた遺伝子操作の現状と課題" TREANDS & TOPICS IN TRANSPLANTATION. 8-1. 18-26 (1997)