ナノセグメント固定化細胞培養基板の調製と幹細胞培養と分化制御

• 研究課題/領域番号: 24560968
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 生物機能・バイオプロセス
• 研究機関: 独立行政法人理化学研究所 (2014); 独立行政法人国立成育医療研究センター (2012-2013)
• 研究代表者: 樋口 亜紺 独立行政法人理化学研究所, 伊藤ナノ医工学研究室, 研究員 (30189766)
• 研究期間 (年度): 2012-04-01 – 2015-03-31
• 研究課題ステータス: 完了 (2014年度)
• 配分額: 5,460千円 (直接経費: 4,200千円、間接経費: 1,260千円); 2014年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円); 2013年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円); 2012年度: 2,340千円 (直接経費: 1,800千円、間接経費: 540千円)
• キーワード: 幹細胞 / バイオマテリアル / 細胞培養 / ハイドロゲル / 細胞接着因子 / 再生医療 / 表面修飾 / 胚性幹細胞 / 造血幹細胞 / 多能性幹細胞 / 弾性率 / ナノセグメント

研究成果の概要

幹細胞の未分化状態での保持、培養並びに適切な組織細胞への分化誘導は、幹細胞を用いる再生医療に必須である。様々な剛性/弾性を有する基板を作成し、その基板上に細胞接着因子並びにオリゴペプチドを固定化させた基板を調製した。様々なナノセグメント固定化細胞培養基板上において、ES細胞、iPS細胞、造血幹細胞並びに間葉系幹細胞を培養して、未分化状態で培養させる最適な基板の剛性 /弾性並びに最適な細胞接着因子ペプチドあるいは細胞外マトリックス蛋白質を判明させた。さらに、適切な組織細胞（骨芽細胞）への分化効率の高い最適な基板の剛性 /弾性並びに最適な細胞接着因子ペプチドとECMを判明させた。

研究成果

• [雑誌論文] Development of biomaterial surfaces with and without microbial nanosegments (2015)
  • 著者名/発表者名: Abdullah A. Alarfaja and Akon Higuchi
  • 雑誌名: Journal of Polymer Engineering 巻: 35 号: 18 ページ: 501-511
  • DOI: 10.1039/c5tb00447k
  • 査読あり
• [雑誌論文] Reprogramming into induced pluripotent stem cells with aid of small and large molecules without use of genetic materials (2015)
  • 著者名/発表者名: A. Higuchi, Q.-D. Ling
  • 雑誌名: Laboratory Investigation 巻: 95 号: 1 ページ: 26-42
  • DOI: 10.1038/labinvest.2014.132
  • 査読あり / オープンアクセス / 謝辞記載あり
• [雑誌論文] Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules (2014)
  • 著者名/発表者名: S. S. Kumar,* A. A. Alarfaj, A. Higuchi
  • 雑誌名: International Journal of Molecular Science 巻: 15 号: 12 ページ: 23418-23447
  • DOI: 10.3390/ijms151223418
  • 査読あり / オープンアクセス / 謝辞記載あり
• [雑誌論文] External stimulus-responsive biomaterials designed for the culture and differentiation of ES, iPS, and adult stem cells (2014)
  • 著者名/発表者名: A. Higuchi, Q.-D. Ling
  • 雑誌名: Progress in Polymer Science 巻: 39 号: 9 ページ: 1585-1613
  • DOI: 10.1016/j.progpolymsci.2014.05.001
  • 査読あり / 謝辞記載あり
• [雑誌論文] Design of polymeric materials for culturing human pluripotent stem cells: Progress toward feeder-free and xeno-free culturing (2014)
  • 著者名/発表者名: A. Higuchi, Q.-D. Ling
  • 雑誌名: Progress in Polymer Science 巻: 39 号: 7 ページ: 1348-1374
  • DOI: 10.1016/j.progpolymsci.2014.01.002
  • 査読あり / 謝辞記載あり
• [雑誌論文] Suppression of cancer-initiating cells and selection of adipose-derived stem cells cultured on biomaterials having specific nanosegments (2014)
  • 著者名/発表者名: T. Kao, A. Higuchi
  • 雑誌名: Journal of Biomedical Material Research B 巻: 102 号: 3 ページ: 463-476
  • DOI: 10.1002/jbm.b.33024
  • 査読あり
• [雑誌論文] Preparation of induced pluripotent stem cells on dishes grafted on oligopeptide under feeder-free conditions (2014)
  • 著者名/発表者名: A. Higuchi, F.-L. Lin
  • 雑誌名: Journal of the Taiwan Institute of Chemical Engineers 巻: 45 号: 2 ページ: 295-301
  • DOI: 10.1016/j.jtice.2013.06.022
  • 査読あり
• [雑誌論文] Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes (2014)
  • 著者名/発表者名: D.-C. Chen, L.-Y. Chen, A. Higuchi
  • 雑誌名: Biomaterials 巻: 35 号: 14 ページ: 4278-4287
  • DOI: 10.1016/j.biomaterials.2014.02.004
  • 査読あり / 謝辞記載あり
• [雑誌論文] Hemocompatibility of Polyampholyte Copolymers with Well-defined Charge-bias in Human Blood (2014)
  • 著者名/発表者名: Shih YJ, Chang Y, Higuchi A
  • 雑誌名: Langmuir 巻: 30 号: 22 ページ: 6489-6496
  • DOI: 10.1021/la5015779
  • 査読あり
• [雑誌論文] Surface zwitterionization of titanium for a general bio-inert control of plasma proteins, blood cells, tissue cells, and bacteria (2014)
  • 著者名/発表者名: Y Chang, A Higuchi
  • 雑誌名: Langmuir 巻: 30 号: 25 ページ: 7502-7512
  • DOI: 10.1021/la500917s
  • 査読あり
• [雑誌論文] Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability (2014)
  • 著者名/発表者名: Fukawatase Y, Toyoda M, Okamura K, Nakamura K, Nakabayashi K, Takada S, Yamazaki-Inoue M, Masuda A, Nasu M, Hata K, Hanaoka K, Higuchi A, Takubo K, Umezawa A
  • 雑誌名: Sci. Rep. 巻: 4 号: 1 ページ: 5421-5421
  • DOI: 10.1038/srep05421
  • 査読あり / オープンアクセス
• [雑誌論文] Introducing mixed-charge copolymers as wound dressing biomaterials (2014)
  • 著者名/発表者名: hong JF, Chang Y and Higuchi 1
  • 雑誌名: ACS Applied Material Interfaces 巻: 6 号: 12 ページ: 9858-9870
  • DOI: 10.1021/am502382n
  • 査読あり
• [雑誌論文] Surface zwitterionization of poly(vinylidene fluoride) microfiltration membranes via reversible self-assembled hydrophobic-driven coating for the improved blood compatibility (2014)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Journal of Membrane Science 巻: 454 ページ: 253-263
  • DOI: 10.1016/j.memsci.2013.11.050
  • 査読あり
• [雑誌論文] Physical cues of biomaterials guide stem cell differentiation fate (2013)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Chemical Reviews 巻: 113 号: 5 ページ: 3297-3328
  • DOI: 10.1021/cr300426x
  • 査読あり
• [雑誌論文] Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells (2013)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Drug Design, Development and Therapy 巻: 7 ページ: 491-502
  • DOI: 10.2147/dddt.s45890
  • 査読あり
• [雑誌論文] Biofouling-resistance control of expanded poly(tetrafluoroethylene) membrane via atmospheric plasma-induced surface PEGylation (2013)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Journal of Membrane Science 巻: 439 ページ: 48-57
  • DOI: 10.1016/j.memsci.2013.03.041
  • 査読あり
• [雑誌論文] The combined influence of substrate elasticity and surface grafted molecules on the ex vivo expansion of hematopoietic stem and progenitor cells (2013)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Biomaterials 巻: 34 号: 31 ページ: 7632-7644
  • DOI: 10.1016/j.biomaterials.2013.07.002
  • 査読あり
• [雑誌論文] Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells, Drug Design (2013)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Drug Design, Development and Therapy 巻: 7 ページ: 70-80
  • 査読あり
• [雑誌論文] Hemocompatibile Control of Sulfobetaine-Grafted Polypropylene Fibrous Membranes in Human Whole Blood via Plasma-Induced Surface Zwitterionization (2012)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Langmuir 巻: 28 号: 51 ページ: 17733-17742
  • DOI: 10.1021/la3036902
  • 査読あり
• [雑誌論文] Wnt signal pathway network genes expression in cell reprogramming and maintenance of pluripotency (2012)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Journal of Tissue Engineering and Regerative Medicine 巻: 6 ページ: 245-245
  • 査読あり
• [雑誌論文] The Isolation and Differentiation of Human Adipose-Derived Stem Cells Using Membrane Filtration (2012)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Biomaterials 巻: 33 号: 33 ページ: 8228-8239
  • DOI: 10.1016/j.biomaterials.2012.08.027
  • 査読あり
• [雑誌論文] Biomimetic Cell Culture Proteins as Extracellular Matrices for Stem Cell Differentiation (2012)
  • 著者名/発表者名: 樋口亜紺、梅澤明弘
  • 雑誌名: Chemical Reviews 巻: 112 号: 8 ページ: 4507-4540
  • DOI: 10.1021/cr3000169
  • 査読あり
• [雑誌論文] PEGylation of anti-biofouling polysulfone membranes via liquid-and vapor-induced phase separation processing (2012)
  • 著者名/発表者名: A. Venault, Y. Chang, D. Wang, D. Bouyer, A. Higuchi, J. Lai
  • 雑誌名: J. Membr Sci 巻: (in press) ページ: 47-57
  • DOI: 10.1016/j.memsci.2012.02.019
  • 査読あり
• [雑誌論文] Effect of the surface density of nanosegments immobilized on culture dishes on ex vivo expansion of hematopoietic stem and progenitor cells from umbilical cord blood (2012)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Acta Biomaterialia 巻: 8 号: 5 ページ: 1749-1758
  • DOI: 10.1016/j.actbio.2012.01.002
  • 査読あり
• [雑誌論文] Bioadhesive Control of Plasma Proteins and Blood Cells from Umbilical Cord Blood onto the Interface Grafted with Zwitterionic Polymer Brushes (2012)
  • 著者名/発表者名: 樋口亜紺
  • 雑誌名: Langmuir 巻: 28 号: 9 ページ: 4309-4317
  • DOI: 10.1021/la203504h
  • 査読あり
• [学会発表] Feeder-free Culture and Reprogramming of Human iPSCs on Dishes Grafted with Cell Adhesion Peptides and Having Different Elasticity (2015)
  • 著者名/発表者名: Akon Higuchi
  • 学会等名: Pan Pacific Symposium on Stem Cells and Cancer Research (8th PPSSC)
  • 発表場所: HsinChu, Taiwan
  • 年月日: 2015-04-11 – 2015-04-13
  • 招待講演
• [学会発表] Physical Cues of Biomaterials Guide Stem Cell Fate of Proliferation and Differentiation (2014)
  • 著者名/発表者名: Akon Higuchi
  • 学会等名: 2014 Tissue Engineering and Regenerative Medicine International Society-America Meeting (TERMIS-AM 2014)
  • 発表場所: Washington DC, USA
  • 年月日: 2014-12-13 – 2014-12-16
• [学会発表] Physical Cues of Biomaterials on Proliferation and Differentiation of Stem Cells (2014)
  • 著者名/発表者名: Akon Higuchi
  • 学会等名: 2014 International Symposium of Materials on Regenerative Medicine (ISOMRM 2014)
  • 発表場所: Taiyuan, Taiwan
  • 年月日: 2014-08-27 – 2014-08-29
  • 招待講演
• [学会発表] Biomaterials for Stem Cell Culture: Effect of Physical Cues of Biomaterials on Proliferation and Differentiation of Stem Cells (2014)
  • 著者名/発表者名: Akon Higuchi
  • 学会等名: International Union of Materials Research Societies International Conference in Asia 2014 (IUMRS-ICA 2014)
  • 発表場所: Fukuoka, Japan
  • 年月日: 2014-08-24 – 2015-08-30
  • 招待講演
• [学会発表] Biomaterials for Stem Cell Culture and Purification: Effect of Physical Cues of Biomaterials on Proliferation of Stem Cells (2014)
  • 著者名/発表者名: Akon Higuchi
  • 学会等名: National Institute for Materials Science (NIMS) Conference 2014
  • 発表場所: Tsukuba, Japan
  • 年月日: 2014-07-01 – 2014-07-03
  • 招待講演
• [学会発表] The Isolation and Differentiation of Human Adipose-Derived Stem Cells Using Membrane Filtration (2013)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: The 13th Pacific Polymer Conference
  • 発表場所: 高雄, 台湾
  • 招待講演
• [学会発表] Purification and Differentiation of Human Adipose-Derived Stem Cells through Porous Polymeric Membranes by Filtration Method (2013)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: International Membrane Conference in Taiwan 2013 & 2013 The 5th Cross-strait Senior Conference on Membrane Science &Technology
  • 発表場所: 桃園, 台湾
  • 招待講演
• [学会発表] The Isolation and Differentiation of Human Adipose-Derived Stem Cells Using Membrane Filtration Method (2013)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: TERMIS-AM 2013 Conference
  • 発表場所: Atlanta, USA
• [学会発表] Purification and Differentiation of Human Adipose-Derived Stem Cells by Filtration Method through Hybrid Membranes (2013)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: TERMIS-AP 2013 Annual Conference
  • 発表場所: Wuzhen, China
• [学会発表] The Isolation and Differentiation of Human Adipose-Derived Stem Cells by Filtration Method through Porous Polymeric Membranes (2013)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 8th Annual Translational Stem Cell Research Conference
  • 発表場所: New York, USA
• [学会発表] Effect of the surface density of nanosegments immobilized on culture dishes on ex vivo expansion of hematopoietic stem and progenitor cells from umbilical cord blood (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: Innovative Biotechnology for a green world and beyond (IBS2012)
  • 発表場所: Daegu, Korea
  • 招待講演
• [学会発表] The isolation and differentiation of human adipose-derived stem cells using membrane filtration through surface-modified polyurethane membrane (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: The 12th Asian BioCeramics Symposinm (ABC-2012)
  • 発表場所: Tainan, Taiwan
  • 招待講演
• [学会発表] Stem cell fate of differentiation is determined by combination of elasticity of cell culture matrix and extracellular matrix grafted on the cell culture matrix (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 2012 International Symposium on Recent Advances in Stem Cells and Cancer
  • 発表場所: Kaohsiung, Taiwan
• [学会発表] Drug Resistance Cells of Colon Cancer Cells Enhanced Production of Carcinoma Embrionic Antigen, But Are Not Cancer-Initiating Cells (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 2012 International Symposium on Recent Advances in Stem Cells and Cancer
  • 発表場所: Kaohsiung, Taiwan,
• [学会発表] Purification and Differentiation of Human Adipose-Derived Stem Cells by Membrane Filtraion Method (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 2012 International Symposium on Recent Advances in Stem Cells and Cancer
  • 発表場所: Kaohsiung, Taiwan,
• [学会発表] Osteoblast differentiation of amniotic fluid-derived stem cells irradiated with visible light (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 3rd TERMIS World Congress 2012
  • 発表場所: Vienna, Austria
• [学会発表] Effect of the surface density of nanosegments immobilized on culture dishes on ex vivo expansion (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 3rd TERMIS World Congress 2012
  • 発表場所: Vienna, Austria
• [学会発表] Xeno-free preparation of iPS cells on synthetic dishes grafted with vitronectin (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: The New York Stem Cell Foundation’s Seven Annual Translational Stem Cell Research Conference
  • 発表場所: New York, USA
• [学会発表] Drug resistance cells of colon cancer cell line enhanced production of carcinoma embryonic antigen, but are not cancer-initiating cells (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 2012 International Symposium of Materials on Regenerative Medicine (2012 ISOMRM)
  • 発表場所: Taipei, Taiwan
• [学会発表] Generation of Induced Pluripotent Stem Cells on Dishes Grafted with Vitronectin Segments under Feeder-layer Free Condition (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 2012 International Symposium of Materials on Regenerative Medicine (2012 ISOMRM)
  • 発表場所: Taipei, Taiwan
• [学会発表] Effect of the Surface Density of Nanosegments Immobilized on Culture Dishes on Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells from Umbilical Cord Blood (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: ACS 244th National Meeting
  • 発表場所: Philadelphia, USA
• [学会発表] Purification and Differentiation of Adipose-derived Stem Cells Separated by A Membrane Filtration Method from Adipose Tissue (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: The 7th Conference of Aseanian Membrane Society (AMS7)
  • 発表場所: Busan, Korea
• [学会発表] Effect of nanosegments on ex vivo expansion of hematopoietic stem and progenitor cells cultured on surface having several nanosegments (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 10th Annual Meeting of International Society for Stem Cells (ISSCR)
  • 発表場所: Yokohama, Japan
• [学会発表] Effect of the surface density of nanosegments immobilized on culture dishes on ex vivo expansion of hematopoietic stem and progenitor cells from umbilical cord blood (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 10th Annual Meeting of International Society for Stem Cells (ISSCR)
  • 発表場所: Yokohama, Japan
• [学会発表] Differentiation ability and pluripotency of amniotic fluid-derived stem cells cultured on extracellular matrix-immobilized surface (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 10th Annual Meeting of International Society for Stem Cells (ISSCR)
  • 発表場所: Yokohama, Japan
• [学会発表] Purification of human adipose tissue-derived stem cells by membrane filtration method (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 10th Annual Meeting of International Society for Stem Cells (ISSCR)
  • 発表場所: Yokohama, Japan
• [学会発表] Purification and depletion of cancer-initiating (cancer stem) cells cultured on biomaterials having nanosegments (2012)
  • 著者名/発表者名: 樋口亜紺
  • 学会等名: 10th Annual Meeting of International Society for Stem Cells (ISSCR)
  • 発表場所: Yokohama, Japan
• [図書] Taylor & Francis (2014)
  • 著者名/発表者名: 樋口亜紺
  • 総ページ数: 50
  • 出版者: Encyclopedia of Biomedical Polymers and Polymeric Biomaterials
• [図書] Encyclopedia of Biomedical Polymers and Polymeric Biomaterials (2014)
  • 著者名/発表者名: 樋口亜紺 (Ed. M. Mishra)
  • 総ページ数: 400
  • 出版者: Taylor & Francis
• [図書] Encyclopedia of Membrane Science and Technology (2013)
  • 著者名/発表者名: 樋口亜紺
  • 総ページ数: 20
  • 出版者: Wiley-Blackwell
• [図書] Encyclopedia of metalloproteins (2013)
  • 著者名/発表者名: 樋口亜紺
  • 総ページ数: 30
  • 出版者: Springer-Verlag
• [図書] Springer-Verlag (2013)
  • 著者名/発表者名: 樋口亜紺(Eds. Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov)
  • 総ページ数: 400
  • 出版者: Encyclopedia of metalloproteins
• [図書] Wiley-Blackwell (2013)
  • 著者名/発表者名: 樋口亜紺(Ed. Eric M. Hoek)
  • 総ページ数: 500
  • 出版者: Encyclopedia of Membrane Science and Technology