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Design of Cell-Recognizable Nano-device and Application to Biosensing and Tissue-engineering

Research Project

Project/Area Number 15100008
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biological material science
Research InstitutionTokyo Institute of Technology

Principal Investigator

AKAIKE Toshihiro  Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Professor, 大学院生命理工学研究科, 教授 (30101207)

Co-Investigator(Kenkyū-buntansha) WATANABE Toshiyuki  Tokyo University of Agriculture and Technology, Institute of Symbiotic Science and Technology, Professor, 大学院共生科学技術研究部, 教授 (10210923)
HARADA Ichiro  Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Assistant Professor, 大学院生命理工学研究科, 助手 (00361759)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥120,510,000 (Direct Cost: ¥92,700,000、Indirect Cost: ¥27,810,000)
Fiscal Year 2006: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2005: ¥31,590,000 (Direct Cost: ¥24,300,000、Indirect Cost: ¥7,290,000)
Fiscal Year 2004: ¥28,080,000 (Direct Cost: ¥21,600,000、Indirect Cost: ¥6,480,000)
Fiscal Year 2003: ¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
KeywordsRegenerative medicine / Tissue engineering / Extracellular matrix / Cellular recognition / Nano-probe / Genetic engineering / Nano-micell / Nano / Micro fabrication / 肝細胞 / ナノ粒子 / マトリクスデバイス / 光重合 / 2光子吸収 / 2光子励起重合 / Computer-Aided Matrix Biology(CAMB) / ナノファイバー / 二光子励起法 / 細胞認識ナノ素子 / パターニング基質 / アレイ状ポストゲル / 細胞培養 / 動画解析システム / 再生医工学 / ナノ微細加工
Research Abstract

In our research, we have designed cell-recognizable nano-probe to analyze cellular behavior in vitro and regulate thme as in vivo. Final goal of our project is to create nano-regulated circumstances of the cells in vitro by using designed nano-probe which have a potential for regenerative medicine and cell-targetting diagnosis and therapy. Bionanothechnology are based on the research objectives. Cell-Matrices engineering are established by our group to regulate the functions of ES-cells as well as hepatocytes using newly-engineered sugar-carrying polymers and chimeric proteins such as E-cadherin Fc, EGF-Fc, LIF-Fc and so on. Nano/micro patterning, probes/carriers technology and biomaterials were developed for dynamic measurements and regulations of cells. The nano carriers technology of carbonate apatite was also established for highly efficient delivery of DNAs, RNAs, proteins and drugs into intra-cellar domain.
We have successfully achieved three major goal. They are, 1. Designing nov … More el cell-recognizable probe as genetically-engineered matrices and application to the cell processing, 2. Designing biocompatible nano-carrier system for targeted cell therapy, 3. Designing nano/ micro 3D patterned culture substrate using two photon polymerization method. For first step, we have designed chimeric proteins which owns cell-recognizable domain and IgG-Fc domain. We found Fc domain successfully allows to anchore nano-probe to any kide of hydrophobic substrate ranging from polystyrene dish to the nano-fiobers. For cell-recognizable domain we tested ranging from cell-cell adhesion proteins such E-cadherin and N-cadherin to cytokines such as EGF and LIF. Any type of ligand we design, the cells successfully recognized them and we found they could regulate cells as we designed. For the next step, we found each of genetically engineered such chimeric proteins were possible to use as nano-probes. We have applied the cell-recognizable proteins for drug/ gene delivery system for targeted cell therapy, and for local stimulation to thte cultured cells. We found our nano-probes could achieve each of the goal. Finally, we desinged nano-regulated culture substrate by using two-photon initiate polymerizatin method. In our project, culture substrate could be fabricated with resolution of 180nm, and also cell could be cultured on the substrate. The substrate we fabricated could achieved to analyze cellular dynamic behavior. Less

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (38 results)

All 2007 2006 2005 2004 Other

All Journal Article (26 results) Book (4 results) Patent(Industrial Property Rights) (1 results) Publications (7 results)

  • [Journal Article] Embryonic undifferentiated cells show scattering activity on a surface coated with immobilized E-cadherin.2007

    • Author(s)
      Nagaoka, M., Ise, H., Harada, I., Koshimizu, U., Maruyama, A., Akaike, T
    • Journal Title

      Biochem. Biophys. Res. Commun. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primary hepatocyte survival on non-integrin-recognizable matrices without the activation of Akt signaling.2007

    • Author(s)
      T.Hoshiba, H.Nagahara, C-S.Cho, Y.Tagawa, T.Akaike
    • Journal Title

      Biomaterials 28

      Pages: 1093-1104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.2007

    • Author(s)
      I.Harada, T.Akaike
    • Journal Title

      J. Biomed. Mater. Res. 80

      Pages: 123-130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Embryonic undifferentiated cells show scattering activity on a surface coated with immobilized E-cadherin.2007

    • Author(s)
      Nagaoka, M., Ise, H., Harada, I., Koshimizu, U., Maruyama, A.Akaike, T
    • Journal Title

      Biochem.Biophys.Res.Commun. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.2007

    • Author(s)
      I.Harada, Kim SG, Cho CS, Kurosawa K, T.Akaike
    • Journal Title

      J.Biomed.Mater.Res. 80

      Pages: 123-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.2007

    • Author(s)
      I.Harada, T.Akaike
    • Journal Title

      J. Biomed. Mater. Res. A. 80

      Pages: 123-30

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Primary hepatocyte survival on non-integrin-recognizable matrices without the activation of Akt signaling.2007

    • Author(s)
      T.Hoshiba, H.Nagahara, C-S.Cho, Y.Tagawa, T.Akaike
    • Journal Title

      Biomaterials. 28

      Pages: 1093-1104

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of photo-immobilization of epidermal growth factor on the cellular behaviors.2006

    • Author(s)
      K.Ogiwara, M.Nagaoka, C-S.Cho, T.Akaike
    • Journal Title

      Biochem. Biophys. Res. Commun. 345

      Pages: 255-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] E-cadherin-coated plates maintain pluripotent ES cells without colony formation.2006

    • Author(s)
      M.Nagaoka, U.Koshimizu, S.Yuasa, F.Hattori, H.Chen, T.Tanaka, M.Okabe, K.Fukuda, T.Akaike
    • Journal Title

      PLoS ONE 1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of photo-immobilization of epidermal growth factor on the cellular behaviors.2006

    • Author(s)
      K.Ogiwara, M.Nagaoka, C-S.Cho, T.Akaike
    • Journal Title

      Biochem.Biophys.Res.Commun. 345

      Pages: 255-259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells.2006

    • Author(s)
      K.Kutsuzawa, E.H.Chowdhury, M.Nagaoka, K.Maruyama, Y.Akiyama, T.Akaike
    • Journal Title

      Biochem. Biophys. Res. Commun. 350

      Pages: 514-520

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Epidermal growth factor signaling for matrix-dependent cell proliferation and differentiation in primary cultured hepatocyte.2006

    • Author(s)
      S-H.Kim, T.Akaike
    • Journal Title

      Tissue Engineering 13

      Pages: 601-609

    • Related Report
      2006 Annual Research Report
  • [Journal Article] E-cadherin-coated plates maintain pluripotent ES cells without colony formation.2006

    • Author(s)
      M.Nagaoka, U.Koshimizu, S.Yuasa, F.Hattori, H.Chen, T.Tanaka, M.Okabe, K.Fukuda, T.Akaike
    • Journal Title

      PLoS ONE 1,

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fabrication of elastic substrates for tissue engineering by two-photon initiated polymerization2005

    • Author(s)
      Kimura N., Watanabe T., Totani K., Oguni A., Harada I., Akaike T.
    • Journal Title

      Nonlinear Optics, Quantum Optics 34

      Pages: 203-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adsorption behaviors of poly(N-p-vinylbenzyl-4-o-b-d-galactopyranosyl-[1→4]-d-gluconamide) by quartz-crystal microbalance.2005

    • Author(s)
      Takei R., Seo S.J., Cho C.S, Okahata Y., Akaike T.
    • Journal Title

      Colloids and Surfaces B : Biointerfaces, 42

      Pages: 137-140

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A Bio-Recognition Device Developed Onto Nano-Crystals of Carbonate Apatite for Cell-Targeted Gene Delivery.2005

    • Author(s)
      Chowdhury E.H., Akaike T.
    • Journal Title

      Biotechnology and Bioengineering 90

      Pages: 414-419

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Albumin and urea production by hepatocytes cultured on extracellular matrix proteins-conjugated poly(vinyl alcohol) membranes2005

    • Author(s)
      Higuchi A., Kurihara M., Kobayashi K., Cho C-S., Akaike T., Hara
    • Journal Title

      J.Biomater.Sci.Polymer Edn. 16

      Pages: 847-860

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hepatocyte Adhesion on a Poly [N-p-vinylbenzyl-4-O-b-D-galactopyranosyl-D-glucoamide]-Coated Poly(L-lactic acid )Surface.2005

    • Author(s)
      Lee J.S., Kim S.H., Kim Y.J., Akaike T., Kim S.C
    • Journal Title

      Biomacromolecules 6

      Pages: 1906-1911

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mammalian integrin-targeted gene delivery : A common approach for advanced viral and non-viral vectors.2005

    • Author(s)
      Chowdhury E.H., Akaike T.
    • Journal Title

      Gene.Ther.Mol.Biol. 9

      Pages: 431-444

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fabrication of Elastic Substrates for Tissue Engineering by Two-Photon Initiated Polymerization.2005

    • Author(s)
      Kimura T, Watanabe T, Totani K, Oguni A, Harada I, Akaike T.
    • Journal Title

      Nonlinear Optics, Quantum Optics. 34

      Pages: 203-206

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hepatocyte behavior on synthetic glycopolymer matrix : inhibitory effect of receptor-ligand binding on hepatocyte spreading.2005

    • Author(s)
      S-H.Kim, T.Hoshiba, T.Akaike
    • Journal Title

      Biomaterials 25

      Pages: 1813-1823

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High-efficiency gene delivery for expression in mammalian cells by nanoprecipitates of Ca-Mg phosphate.2004

    • Author(s)
      E.H.Chowdhury, M.Kunou, M.Nagaoka, A.K.Kundu, T.Hoshiba, T.Akaike
    • Journal Title

      Gene 341

      Pages: 77-82

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Xyloglucan as a synthetic extracellular matrix for hepatocyte attachment.2004

    • Author(s)
      S.J.Seo, I-K.Park, M-K.Yoo, M.Shirakawa, T.Akaike, C.S.Cho
    • Journal Title

      J.Biomater.Sci.Polymer Edn. 15

      Pages: 1375-1387

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effective Hepatocyte Transplantation Using Rat Hepatocytes with Low Asialoglycoprotein Receptor Expression.2004

    • Author(s)
      H.Ise, T.Nikaido, N.Negishi, N.Sugihara, F.Suzuki, T.Akaike, U.Ikeda
    • Journal Title

      Am.J.Pathol. 165

      Pages: 501-510

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synthesis and their Two-Photon Absorption Measurement of Novel Push-Pull Fluorophores2004

    • Author(s)
      Y.Lu, F.Hasegawa, Y.Kawazu, K.Totani, T.Watanabe
    • Journal Title

      J.Lumin. 110

      Pages: 1-10

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Highly efficient two-photon initiated polymerization in solvent by using novel two-photon chromophore and co-initiators2004

    • Author(s)
      Y.Lu, F.Hasegawa, S.Ohkuma, T.Goto, S.Fukuhara, Y.Kawazu, K.Totani, T.Yamashita, T.Watanabe
    • Journal Title

      J.Mater.Chem. 14(9)

      Pages: 1391-1395

    • Related Report
      2004 Annual Research Report
  • [Book] 再生医療の基礎シリーズ4 再生医療のためのバイオエンジニアリング2007

    • Author(s)
      赤池敏宏
    • Total Pages
      226
    • Publisher
      コロナ社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 再生医療の基礎シリーズ4 再生医療のためのバイオエンジニアリング2006

    • Author(s)
      赤池敏宏
    • Total Pages
      222
    • Publisher
      コロナ社
    • Related Report
      2006 Annual Research Report
  • [Book] バイオテクノロジー教科書シリーズ122005

    • Author(s)
      赤池敏宏
    • Total Pages
      173
    • Publisher
      コロナ社
    • Related Report
      2005 Annual Research Report
  • [Book] 材料表面修飾とティッシュエンジニアリング:キメラタンパク質を用いた細胞接着応答の制御 ティッシュエンジニアリング20052005

    • Author(s)
      荻原一隆, 長岡正人, 赤池敏宏
    • Publisher
      日本医学館
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 物質導入担体、物質導入方法及び物質導入用キット2005

    • Inventor(s)
      赤池 敏宏, Choudhury Fatema
    • Industrial Property Rights Holder
      東京工業大学
    • Filing Date
      2005-08-31
    • Related Report
      2005 Annual Research Report
  • [Publications] S-H.Kim, T.Hoshiba, T.Akaike: "Effect of carbohydrates attached to polystyrene on hepatocyte morphology on sugar-derivatized polystyrene matrices"J.Biomed.Mater.Res.. 67A. 1351-1359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] E.H.Chowdhury, T.Sasagawa, M.Nagaoka, A.K.Kundu, T.Akaike: "Transfecting mammalian cells by DNA/calcium phosphate precipitates : Effect of temperature and pH on precipitation"Analytical Biochemistry. 314. 316-318 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Nagaoka, T.Akaike: "Single amino acid substitution in the mouse IgGl Fc region induces drastic enhancement of the affinity to protein A"Protein Engineering. 16. 243-245 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Hernandez, H.Miura, M.Beristain, T.Ogawa, T.Watanabe, S.Miyata: "Novel Diacetylene-containing Polymers for Second order NLO Applications : Effect of Main chains and Structure Property Relationships"Macromolecular Symp.. 192. 123-133 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S-H.Kim, J-H.Kim, T.Akaike: "Regulation of cell adhesion signaling by synthetic glycoppolymer matrix in primary cultured hepatocyte"FEBS Letters. 553. 433-439 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Lu, F.Hasegawa, T.Goto, S.Ohokuma, S.Fukuhara, Y.Kawazu, K.Totani, T.Yamashita, T.Watanabe: "Highly Sensitive Two-photon Chromophores Applied to Three Dimensional Lithographic Microfabricalion : Design Synthesis and Characterization Towards Two Photon Absorption Cross Section"J.Mater.Chem.. 14(1). 75-80 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 赤池敏宏: "日本産業の推進力「先端技術」『再生医療と人工臓器』"一橋フォーラム. 54 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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