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組織器官形成促進材料

Research Project

Project/Area Number 04204008
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTokyo Institute of Technology

Principal Investigator

赤池 敏宏  東京工業大学, 生命理工学部, 教授 (30101207)

Co-Investigator(Kenkyū-buntansha) 井街 宏  東京大学, 医学部, 助教授 (10010076)
関口 清俊  大阪府立母子保健総合医療センター研究所, 病因病態部, 部長 (50187845)
野一色 泰晴  横浜市立大学, 医学部, 講師 (60033263)
出月 康夫  東京大学, 医学部, 教授 (60081717)
中村 敏一  九州大学, 理学部, 教授 (00049397)
Project Period (FY) 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1992: ¥15,000,000 (Direct Cost: ¥15,000,000)
Keywordsハイブリッド人工臓器 / 人工肝臓 / 人工血管 / 人工基質 / 細胞接着因子 / 細胞増殖因子 / 組織形成
Research Abstract

ハイブリッド人工臓器を開発するためには、生体外(in vitro)において細胞の組織化を制御し、機能発現性と長期生存性の高い培養システムを確立することが重要である。この目的を実現するためには細胞と接着基質(細胞外マトリックス又はそのモデル材料)の間の相互作用を制御し、これと細胞-細胞間相互作用、細胞-増殖因子相互作用の強さとバランスさせることが重要である。本研究では、主として肝臓と血管の組織形成に着目した。赤池らは、既に前年度までに開発してきた肝細胞特異的な人工基質(PVLA)を用いて、肝実質細胞と非実質細胞との混合培養をおこない上皮細胞増殖因子の添加をおこなうことなく生体内肝組織に類似した三次元組織構築を形成させることに成功した。又この形成因子が非実質細胞から分泌されるタンパク質性の因子であることを見出した。中村らは既に発見した肝細胞増殖因子(CHGF)が肝再生因子、腎再生因子として機能することを実証し、HGFが細胞増殖を促進するだけではなく多くの臓器の形態形成を誘導する因子であることを見出した。野一色らは人工血管の埋込み後の新生内膜化を促進する方法として種々の自家組織片を繊維素材に播種後移植する方法を開発し、生体内増殖因子の産生機構をうまく利用することに成功した。関口らは遺伝子組替法を利用して各種の細胞接着因子の分子認識メカニズムの解明と一分子内に複数種の活性ドメインの導入に成功した。他の研究グループもハイブリッド人工臓器の設計に関わる重要な知見を明らかにした。

Report

(1 results)
  • 1992 Annual Research Report
  • Research Products

    (64 results)

All Other

All Publications (64 results)

  • [Publications] A.Kobayashi,K.Kobayashi,T.Akaike: "¨Control of Adhesion and Detachment of Parenchymal Liver Cells Using Lactose-carrying Polystyrene as Substratum¨" J.Biomater.Sci.3,. 499-508 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 由良 洋文,赤池 敏宏: "″細胞認識作用を有する接触基質の設計とその細胞工学応用″" 応用細胞生物学研究. 9. 62-79 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 後藤 光昭,赤池 敏宏: "″細胞認識性分子の設計とターゲット療法への応用″" CURRENT THERAPY(別冊). 10. 996-1003 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 後藤 光昭,小林 明,小林 一清,斎藤 和宏,赤池 敏宏: "″肝細胞認識機能を有する超分子構造型ドラッグキャリアの開発とその応用″" Drug Delivery System,. 7(3). 173-179 (1992)

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      1992 Annual Research Report
  • [Publications] T.Akaike;: "¨Design of cell recognizing polymers and its application to missile drugs¨" Capsugel Symposia series;. 81-85 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Kobayashi,A.Koyama,H.Goto,K.Kobayashi Chia-Wun Chang,T.Akaike: "¨Glucose transporter-mediated dynamic attachment of erythrocytes onto a reducing glucose-carrying polystyrene¨" Proc.Jpn.Acad.,.

    • Related Report
      1992 Annual Research Report
  • [Publications] M.GOTO,A.KOBAYADHI,K.KOBAYADHI,K.SAITO,and T.AKAIKE: "Model Study of Hepatocyte Targeting Polymeric Super Molecular Assembly as Drug Carrier¨" CHEMISTRY LETTERS. 1(241). 123-126 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 戸辺 成四郎,武井 由香,久々宮 岳志,小林 明,小林 一清,赤池 敏宏: "“肝実質細胞-非実質細胞混合培養によるハイブリッド型人工肝臓の高機能化-レセプター仲介型人工マトリックスの臓器工学への応用-"" 人工臓器. 21(1). 217-221 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 戸辺 成四郎,武井 由香,赤池 敏宏,竹下 和良,小玉 正智: "“PVLAコートホローファイバーモジュール内での肝細胞多層集合体の形成と休外循環型ハイブリッド人工肝臓への応用"" 人工臓器. 21(3). 1045-1049 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 藤本 幸之進,近藤 慶之,武井 由香,戸辺 成四郎,赤池 敏宏: "“両性電解質型ポリアミノ酸と初代培養肝細胞との相互作用"" 人工臓器. 21(1). 212-216 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小林 明,武井 由香,戸辺 成四郎,後藤 光昭,小林 一清,赤池 敏宏: "肝細胞の分化増殖を制御するアシアロ糖タンパクモデルの接着基質の設計とその応用"" 人工臓器. 21(3). 1060-1064 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tobe,Y.Takei,K.Kobayashi,and T.Akaike: "¨Receptor-Mediated Formation of Multilayer Aggregates of Primary Cultured Adult Rat Hepatocytes on Lactose-Substituted Polystyrene¨" Biochem,Biophys.184. 225-230 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kugumiya,A.Yakawa,A.Maeda,H.Nomoto,S.Tobe,T.Matsuda,T.Ohnishi,K.Kobayashi,T.Akaike: "¨Investigation of Dynamic Behaviors of Asialoglycoprotein Receptors of Hepatocytes Using aLatex Probe whose Surface wasCoated with Lactose-Carrying Polysty rene¨" J.Bioactive Compatible Polym.7,. 338-345 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Akaike,S.Tobe,A.Kobayashi,M.Goto,K.Kobayashi: "¨Sesign of Hepatocyte-specific Extracellular Matrices for Hybrid Artificial Liver¨" Gastronterologia Japonica,.

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hatanaka,A.Maruyama,H.Kuzugara,T.Akaike Soo-Chang Song,: "¨A New Synthetic Hypoglycaemic Polysaccharide¨" Biochem.Biophys.1881(1). 16-19 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hatanaka,A.Maruyana Soo-Chang Song.T.Akaike: "¨Novel Reaction Route Including Enzymic Reaction for Stereoselective Synthesis of a Branched Polysaccharide¨" J.Carbohydr.Chem.,. 11(8). 1027-1037 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Kai et al;: "¨Biosynthesis of a Culdlan from Culture Medium Containing 13C-labeled Glucose as Carbon Sources¨" Carbohydr.Res.,.

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Haruyama,N.Adachi,T.Akaike et al: "¨Preparation of Poly(laticacid) Nanospheres Bearing Cell-Specific Saccharides¨" Bioconjugate Chem.,.

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tobe,.K.Kobayashi,Y.Takei,T.Akaike: "¨Tissue Reconstruction in Primary Cultured Rat Hepatocytes on Asialoglycoprotein Model Polymer" Artificial Organs,. 16(5). 526-532 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小林 明,大河原 久子,小林 一清,赤池 敏宏,大森 安恵,後藤 光昭: "″糖を有した合成高分子含有ハイドロゲルのハイブリッド型人工肝臓への応用"" 人工臓器.

    • Related Report
      1992 Annual Research Report
  • [Publications] 竹下 和良,石橋 治昭,戸辺 成四郎,赤池 敏宏,小玉 正智他: "″ホローファイバー型モジュールを用いたコラーゲンゲル内肝細胞高密度灌流培養と体外循環型ハイブリッド人工肝臓への応用″" 人工臓器.

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tobe,K.Kobayashi,Y.Takei,T.Akaike et al: "¨Stimulatory Effect of Nonparenchymal Liver Cells on Formation of Multilayer Aggregates of Adult Rat Hpatocytes Cultured on Lactose-sabstituted Polystyrene," Commun Applied Cell Biol. 11(1). 14-21 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Kobayashe,M.Goto,T.Sekine,A.Masatomo,N.Yamamoto,K.Kobayashi,T.Akaike: "¨Regulation of Differentiation and Proliferation of Rat Hepatocytes by Lactose-Carrying Polystyrene," Artifial Organs¨. 16(6). 654-657 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Chong-Su Cho,T.Kotaka,T.Akaike;: "¨Cell Adhesion onto Bolck Copolymer Langmuir-Blodgett Films¨" J.Biomed Mater Res.27,. 199-206 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] R.Takezawa,K.Shinzawa,Y.Watanabe,T.Akaike;: "¨Determination of Mouse Major Asialoglycoprotein Receptor c DNA Sequence¨" Biochim.Biophys.Acta.

    • Related Report
      1992 Annual Research Report
  • [Publications] 赤池 敏宏: "″小口径人工血管の開発″" 高分子. 41(4). 265 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 後藤 光昭,赤池敏宏: "″細胞認識性分子を有する超分子集合休型薬物運搬体の設計とターゲット療法への応用″" 化学と工業. 45(11. 2052-2055

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Noishiki,C.Hata,R.Tu,SH.Shen,D.Lin RW Sung,T.Witzel: "The developmnet ofa pliable biological valved conduit." J.Europ.Artif.Organs.

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Noishiki,Y Yamane,Y Tomizawa,T Okoshi,S Satoh,RH Wildevuur: "Rapid endothelialization of vascular prostheses seeded with autiolgous venous tissue fragments." J.Thorac.Cardiovasc.Surg.104. 770-778 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Noishike,Y Yamane,Y Tomizawa,T Okoshi S,S Satoh,T kosuge: "A method to reduce thrombogenicity of a graft fpr small ddameter arterial substitution seeded with autologous tissue fragments." J.Am.Soc.Artif.Intern.Organs. 38. 148-162 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Tomizawa,Y Noishiki,T Okoshi,H Koyanagi,: "Development of a polyepoxy compound cross-linked hetelorogous connective tissue tube." J.Am.Soc.Artif.Intern.Organs. 38. 357-361 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Noishiki,Y Tomizawa,Y Yamane,T Okoshi,S Satoh,A Matsumoto: "Acceleration of neointima formation in vascular prostheses by transplantation of autologous venous tissue fragments.Application of small diameter graft" J.Thorac.Cardiovasc.Surg.

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Tomizawa,MR Moon,Y Noishiki: "Biological vascular grafts in the venous system" J.Thorac.Cardiovasc.Surg.

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Ichihara-Tanaka他: "Matrix assembly of recombinant fibronectin polypeptide consisting of amino-terminal 70 KDa and carboxyl-terminal 37 KDa regions" FEBS letters. 299. 155-158 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hashino他: "Engineering of Artificial Cell Adhesion Proteins by Grafting the Arg-Gly-Asp Cell Adhesive Signal to a Calpastatin Segment" J.Biochem.112. 547-551 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Maeda他: "Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin" J.Biochem.113. 29-35 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] F.Oyama他: "Coordinate oncodevelopmental modulation of altemative splicing of fibroncctin pre-mRNA at ED-A,ED-B,and CSI regions in himan liver tumors" Cancer Research.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shiota,G.,Rohads,D.B.,Wang,T.C.,Nakamura,T.,and Schmidt,E.V.: "Hepatocyte growth factor inhibits growth of hepatocellular cacinoma cells." Proc.Natl.Acad.Sci.USA. 89. 373-377 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumoto,K.,Tajima,H.,Hamanoue,M.,Kohno,S.,Kinoshita,T.,and Nakamura,T.: "Identification and characterization of ¨injurin¨,an inducer of expression of the gene for hepatocyte growth factor." Proc.Natl.Acad.Sci.USA. 89. 3800-3804 (1992)

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      1992 Annual Research Report
  • [Publications] Higuchi,O.,Mizuno,K.,Vande Voude,G.G.,and Nakamura,T.: "Expression of the c-met protooncogene in COS cell sis required for hepatocyte growth factor high affinity binding and mitogenic signal transduction." FEBS Lett.301. 282-286 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ishiki,Y.,Ohnishi,H.,Muto,Y.,Matsumoto,K.,Nakamura,T.: "Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and for potent anti-hepatits action in vivo." Hepatology. 16. 1227-1235 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumoto,K.,Tajima,H.,Okazaki,H.,and Nakamura,T.: "Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-β and glucocorticoids." J.Biol.Chem.267. 24917-24920 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tajima,H.,Matsumoto,K.,and Nakamura,T.: "Regulation of cell growth and motility by hepatocyte growth factor and receptor expression in various cell species." Exp.Cell Res.202. 423-431 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizuno,K.,Takehara,T.,and Nakamura,T.: "Proteolytic activation of single-chain precursor of hepatocyte growth factor by extracellular serine protease." Biochem.Biophys.Res.Commun.189. 1631-1638 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Imachi: "Fabrication of a jellyfish valve for use in an artificial feart" ASAIO Journal. 38. 237-242 (1992)

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      1992 Annual Research Report
  • [Publications] K.Mabuchi: "Changes with respect to time in the in vivo adsorption of plasma proteins onto artifioial heart blood pumps" ASAIO Journal. 38. 237-242 (1992)

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      1992 Annual Research Report
  • [Publications] 井街 宏: "人工心臓用材料の生体適合性" 文部省重点領域研究「機能性材料」ニュース. 21(March). 2-8 (1992)

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      1992 Annual Research Report
  • [Publications] 宮田 哲郎他: "ハイブリッド型人工血管の開発と将来の展望。ー内皮細胞Seeded gvofgの臨床応用に向けてー" 脈管学. 32. 215-219 (1992)

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      1992 Annual Research Report
  • [Publications] 遠藤 俊哉他: "内皮細胞播種人工血管中央部,吻合部の経時的な組織学的相違についての検討" 人工臓器.

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      1992 Annual Research Report
  • [Publications] Shindo,S,et al.: "Perianistomotic findugs of the endothelialall Seedad gnalis at three mouths" ASAIO Journal.

    • Related Report
      1992 Annual Research Report
  • [Publications] 赤池 敏宏,大道 高弘: ""蛋白質を原料とした生物機能素子の研究と現状と将造展望"" (財)新機能素子研究開発協会, (1992)

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      1992 Annual Research Report
  • [Publications] 赤池 敏宏,後藤 光昭,小林 明: ""細胞認識性高分子の設計とミサイルドラッグへの応用"" J.Japan.Soc.Hosp.Pharmacists.,531-534 (1992)

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      1992 Annual Research Report
  • [Publications] 丸山 厚,赤池 敏宏: "“生命工学材料の展望"" ケミカル・エンジニヤリング, 41-48 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 赤池 敏宏,大道 高弘: ""生体分子・細胞の人工材料への固定化制御"マイクロマシン技術による製品小型化・知能化辞典、" 産業調査会, 392-398 (1992)

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      1992 Annual Research Report
  • [Publications] 赤池 敏宏: ""生体適合性材料"ニューマテリアルハンドブック" 昭晃堂,

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      1992 Annual Research Report
  • [Publications] 赤池 敏宏: ""細胞社会"蛋白質核酸酸素特集号" 共立出版,

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Noishiki: "New concepts and development of vascular prostheses.In Advances in cardiovascular Engineering.Ed by Ned HC Hwang" Springer-Verg,Bergium,

    • Related Report
      1992 Annual Research Report
  • [Publications] Y Noishiki,Y Yamane,Y Tomizaws,T Ohoshi S Satoh,M Mo,M Ishii,Y Ichikawa,K Imoto,K Yamamoto,T Kosuge,M Tobe,J Kondo: "Natural antithrombogenic surface made in in vivo for artificial heart.In Artificial Heart 4,Ed by T Akutsu and H Koyanagi" Springer-Verg.Hong Kong,

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      1992 Annual Research Report
  • [Publications] 関口 清俊: "新生化学実験講座 第6巻「生体膜と膜輸送」pp.326-331(分担執筆)" 東京化学同人, 424 (1992)

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      1992 Annual Research Report
  • [Publications] 松山 聡,関口 清俊: "新生化学実験講座 第10巻「血管:内皮と平滑筋」§11・3・2 フィプロネクチン・ビトロネクチン:遺伝子レベル" 東京化学同人,

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      1992 Annual Research Report
  • [Publications] Nizuno,K.and Nakamura,T.: "Molecular characteristics of HGF and gene,and its biochemical aspects.Hepatocyte Growth Factor-Scatter Facto and C-Met Receptor(ed.Goldberg,I.D.)" Birkhauser Verlag, 1-29 (1993)

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      1992 Annual Research Report
  • [Publications] Matsumoto,K.and Nakamura,T.: "Roles of HGF as a pleiotropic factor in organ regeneration.Hepatocyte Growth Factor-Scatter Factor and C-Met Receptor(ed.Goldberg,I.D.)" Birkhauser Verlag, 225-249 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 井街 宏: "人工臓器1992(阿岸鉄三,桜井靖久,高野久輝編)" 中山書店, 317 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Imachi: "Artificial Heart-4(T.Akutsu Ed.)" Springer-Verlag, (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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