長瀬 健一 (ナガセ ケンイチ)

Nagase, Kenichi

写真a

所属(所属キャンパス)

薬学部 薬科学科 創薬物理化学講座 (芝共立)

職名

准教授

総合紹介 【 表示 / 非表示

経歴 【 表示 / 非表示

  • 2005年04月
    -
    2007年03月

    東京女子医科大学, 先端生命医科学研究所, 博士研究員

  • 2007年04月
    -
    2011年03月

    東京女子医科大学, 先端生命医科学研究所, 助教

  • 2011年04月
    -
    2017年03月

    東京女子医科大学, 先端生命医科学研究所, 講師

学歴 【 表示 / 非表示

  • 1996年04月
    -
    2000年03月

    早稲田大学, 理工学部, 応用化学科

    日本, 大学, 卒業

  • 2000年04月
    -
    2002年03月

    早稲田大学, 理工学研究科, 応用化学専攻

    日本, 大学院, 修了, 修士

  • 2002年04月
    -
    2005年03月

    早稲田大学, 理工学研究科, 応用化学専攻

    日本, 大学院, 修了, 博士後期

学位 【 表示 / 非表示

  • 博士(工学), 早稲田大学, 課程, 2005年03月

免許・資格 【 表示 / 非表示

  • 日本分析化学会 液体クロマトグラフィー分析士 初段, 2017年09月

 
 

著書 【 表示 / 非表示

  • 刺激応答性高分子ハンドブック

    長瀬 健一、金澤秀子, 株式会社エヌ・ティー・エス, 2018年12月

    担当範囲: 温度応答性クロマトグラフィー

  • Temperature‐responsive Polymers for Tissue Engineering

    Kenichi Nagase, Masayuki Yamato, Teruo Okano, John Wiley & Sons, 2018年06月

    担当範囲: Temperature‐Responsive Polymers: Chemistry, Properties and Applications

  • Polymer and Biopolymer Brushes: For Materials Science and Biotechnology

    Kenichi Nagase, Teruo Okano, John Wiley & Sons, 2018年01月

    担当範囲: Thermoresponsive Polymer Brushes for Thermally Modulated Cell Adhesion and Detachment

  • バイオマテリアル-その基礎と先端研究への応用

    長瀬 健一、大和雅之, 東京化学同人, 2016年02月

    担当範囲: 細胞シート

  • Encyclopedia of Biocolloid and Biointerface Science 2V Set

    Kenichi Nagase, Teruo Okano, John Wiley & Sons, 2016年

    担当範囲: Bioseparation Using Thermoresponsive Polymers

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論文 【 表示 / 非表示

  • Mixed polymer brush as a functional ligand of silica beads for temperature-modulated hydrophobic and electrostatic interactions

    Nagase K., Kitazawa S., Yamada S., Akimoto A., Kanazawa H.

    Analytica Chimica Acta (Analytica Chimica Acta)  1095   1 - 13 2020年01月

    研究論文(学術雑誌), 共著,  ISSN  00032670

     概要を見る

    © 2019 Elsevier B.V. We developed a mixed polymer brush, which consists of temperature-responsive polymer and cationic polymer modified beads as functional chromatographic matrices, for temperature-modulated multiple hydrophobic and electrostatic interactions. The mixed polymer brush was modified on silica beads through the combination of reversible addition−fragmentation chain transfer (RAFT) polymerization of N,N-dimethylaminopropyl acrylamide (DMAPAAm) and surface initiated atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAm). Zeta potential measurement of the mixed polymer brush revealed that the zeta potential increased with increasing temperature, which was attributed to the exposed PDMAPAAm on the beads arising from the shrinking of PNIPAAm upon increasing the temperature. The prepared beads were used as the packing material of high performance liquid chromatography (HPLC) columns, and the elution behavior of steroids, adenosine nucleotides, and proteins through the column was observed. The retention time of steroids increased with increasing the column temperature because of the dehydration of PNIPAAm in the mixed polymer brush. Adenosine nucleotides were also retained by the columns, which was attributed to the electrostatic interaction with PDMAPAAm in the mixed polymer brush. Several proteins were adsorbed on the column at elevated temperatures because of the enhanced electrostatic interaction of exposed PDMAPAAm and the enhanced hydrophobic interaction resulting from the dehydration of PNIPAAm. By exploiting this unique property, mixtures of proteins could be separated by simply changing the column temperature. These results indicate that the developed mixed polymer brush modified beads would be useful as functional chromatographic packing matrices for thermally-modulated multiple hydrophobic and electrostatic interactions.

  • Thermoresponsive anionic copolymer brush-grafted surfaces for cell separation

    Nagase K., Uchikawa N., Hirotani T., Akimoto A., Kanazawa H.

    Colloids and Surfaces B: Biointerfaces (Colloids and Surfaces B: Biointerfaces)  185 2020年01月

    ISSN  09277765

     概要を見る

    © 2019 Elsevier B.V. Cell separation methods that do not require surface modification of cells are needed in tissue engineering and regenerative medicine. We developed thermoresponsive anionic polymer brushes for cell separation without modification of the cell surfaces. Copolymer brush poly(N-isopropylacrylamide-co-N-tert-butylacrylamide-co-tert-butyl acrylate, P(NIPAAm-co-tBAAm-co-tBA), was prepared on a cover glass plate through activator regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). The tert-butyl group of the copolymer brush was then deprotected and a P(NIPAAm-co-tBAAm-co-acrylic acid (AAc)) brush-modified glass surface was obtained. ARGET-ATRP synthesis achieved polymers with low polydispersity. The negative surface charge of the polymer brush-modified substrates was evaluated using zeta potential measurements and the phase transition temperature of the polymer was modulated between 37–20 °C to perform cell adhesion and detachment, respectively. The adhesion and detachment behavior of cells used in cardiovascular tissue engineering on the thermoresponsive anionic polymer brushes was investigated. Normal human umbilical vein endothelial cells (HUVEC) exhibited prompt detachment from the thermoresponsive anionic polymer brush surfaces. In addition, normal human aortic smooth muscle cells (SMC) exhibited relatively high adhesion on thermoresponsive anionic polymer brush-modified surfaces compared with those modified with thermoresponsive polymer brushes without anionic groups. By utilizing the difference in the cell adhesion and detachment properties of the cell types, a mixture of HUVEC and SMC was separated simply by altering the applied temperature. This result indicated that the prepared thermoresponsive anionic polymer brush-modified glass surface could be used as a tool for the separation of cells in cardiovascular tissue engineering.

  • Phenotypic traits of mesenchymal stem cell sheets fabricated by temperature-responsive cell culture plate: Structural characteristics of MSC sheets

    Nakao M., Kim K., Nagase K., Grainger D., Kanazawa H., Okano T.

    Stem Cell Research and Therapy (Stem Cell Research and Therapy)  10 ( 1 )  2019年11月

     概要を見る

    © 2019 The Author(s). Background: In most stem cell therapy strategies reported to date, stem cells are introduced to damaged tissue sites to repair and regenerate the original tissue structure and function. MSC therapeutic efficacies are inconsistent, largely attributed to transplanted MSC difficulties both in engrafting at tissue sites and in retaining their therapeutic functions from suspension formulations. MSC functional components, including cell adhesion and cell-cell junction proteins, and ECM that contribute to essential cellular therapeutic effects, are damaged or removed by proteolytic enzymes used in stem cell harvesting strategies from culture. To overcome these limitations, methods to harvest and transplant cells without disrupting critical stem cell functions are required. Cell sheet technology, exploiting temperature-responsive cell culture surfaces, permits cell harvest without cell protein damage. This study is focused on phenotypic traits of MSC sheets structurally and functionally to understand therapeutic benefits of cell sheets. Methods/results: This study verified cleaved cellular proteins (vinculin, fibronectin, laminin, integrin β-1, and connexin 43) and increased apoptotic cell death produced under standard trypsin harvesting treatment in a time-dependent manner. However, MSC sheets produced without trypsin using only temperature-controlled sheet harvest from culture plastic exhibited intact cellular structures. Also, MSCs harvested using enzymatic treatment (i.e., chemical disruption) showed higher pYAP expression compared to MSC sheets. Conclusion: Retention of cellular structures such as ECM, cell-cell junctions, and cell-ECM junctions is correlated with human umbilical cord mesenchymal stem cell (hUC-MSC) survival after detachment from cell culture surfaces. Retaining these proteins intact in MSC cultures using cell sheet technology is proposed to enhance stem cell survival and their function in stem cell-based therapy.

  • Temperature-modulated cell-separation column using temperature-responsive cationic copolymer hydrogel-modified silica beads

    Nagase K., Inanaga D., Ichikawa D., Mizutani Akimoto A., Hattori Y., Kanazawa H.

    Colloids and Surfaces B: Biointerfaces (Colloids and Surfaces B: Biointerfaces)  178   253 - 262 2019年06月

    ISSN  09277765

     概要を見る

    © 2019 Elsevier B.V. There is strong demand for cell separation methods that do not decrease cell activity or modify cell surfaces. Here, new temperature-modulated cell-separation columns not requiring cell-surface premodification are described. The columns were packed with temperature-responsive cationic polymer hydrogel-modified silica beads. Poly(N-isopropylacrylamide-co-n-butyl methacrylate-co-N,N-dimethylaminopropyl acrylamide) hydrogels with various cationic moieties were attached to silica-bead surfaces by radical polymerization using N,Nʹ-methylenebisacrylamide as a crosslinking agent. The beads were packed into solid-phase extraction columns, and temperature-dependent cell elution from the columns was found using HL-60 and Jurkat cells. The retention HL-60 and Jurkat cells in columns containing cationic beads at 37 °C was 95.3% to 99.6% and 95.0% to 98.8%, respectively. By contrast, beads without cationic properties exhibited low cell retention (20.6% for HL-60 and 32.5% for Jurkat cells). The cells were mainly retained through both electrostatic and hydrophobic interactions. The retained HL-60 (4.9%) and Jurkat cells (40%) were eluted at 4 °C from the column with a low composition of cationic monomer (DMAPAAm, 1 mol% in copolymer), because the temperature-responsive hydrogels on the beads became hydrophilic, decreasing the hydrophobic interactions between the cells and the beads. A higher number of Jurkat cells than HL-60 cells were eluted because of differences in their electrostatic properties (Jurkat cells: −2.53 mV; HL-60 cells: −20.7 mV). The results indicated that cell retention by the hydrogel-coated beads packed in a solid phase extraction column could be modulated simply by changing the temperature.

  • LAT1-Targeting Thermoresponsive Liposomes for Effective Cellular Uptake by Cancer Cells

    Maekawa-Matsuura M., Fujieda K., Maekawa Y., Nishimura T., Nagase K., Kanazawa H.

    ACS Omega (ACS Omega)  4 ( 4 ) 6443 - 6451 2019年04月

    ISSN  2470-1343

     概要を見る

    © 2019 American Chemical Society. L-type amino acid transporter 1 (LAT1) is a transporter that is more highly expressed in cancer cells compared with normal cells. In the present study, liposomes, composed of egg phosphatidylcholine (EPC) and dioleoyl phosphatidylethanolamine, were modified with LAT1-targeting thermoresponsive polymer, l-tyrosine-conjugated poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)). The cellular uptake of the prepared LAT1-targeting liposomes was evaluated using HeLa cells as a cancer cell model. At temperatures above the polymer's lower critical solution temperature, uptake of the liposomes into cells was observed because the polymer at the liposome surface became hydrophobic and interacted with the cell membrane. Flow cytometry analysis suggested that l-tyrosine-P(NIPAAm-co-DMAAm)-liposomes exhibited markedly increased cellular uptake by HeLa cells compared with that of liposomes not modified with l-tyrosine. This result indicated that cellular uptake of liposomes can be enhanced by the affinity between l-tyrosine and the LAT1 of HeLa cells. The developed functional liposomes, which exhibit both thermoresponsive and LAT1-targeting properties, would be appropriate for temperature-modulated drug delivery and imaging with good targeting ability.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • 効果的な心筋細胞シート移植のためのVEGF徐放ファイバーマットの開発

    長瀬健一, 金澤秀子

    Drug Delivery System (じほう)  34 ( 3 ) 173 - 178 2019年07月

    総説・解説(学術雑誌), 共著,  ISSN  0913-5006

  • 微細構造表面と温度応答性高分子を用いた細胞分離技術の開発

    長瀬, 健一, 宿輪, 理紗, 小沼, 隆大, 大和, 雅之, 武田, 直哉 and 岡野, 光夫

    バイオマテリアル -生体材料- 36 ( 2 ) 158 - 159 2018年04月

    総説・解説(学術雑誌), 共著

  • 積層化細胞シートの移植効率向上を目的とした細胞増殖因子徐放ファイバーマットの開発

    長瀬, 健一, 関根, 秀一, 清水, 達也, 金澤, 秀子, 岡野, 光夫, Lee, Seung Jin and 大和, 雅之

    Bioindustry (CMC出版)  35 ( 4 ) 36 - 45 2018年04月

    総説・解説(学術雑誌), 共著

  • 温度応答性高分子ブラシの精密設計とバイオセパレーションへの応用

    長瀬 健一, 岡野光夫, 金澤秀子

    高分子論文集 75 ( 2 ) 143 - 154 2018年02月

    総説・解説(学術雑誌), 共著

  • 精密重合法によるナノバイオインターフェイスの構築とバイオセパレーションへの応用

    長瀬 健一

    バイオマテリアル-生体材料- (日本バイオマテリアル学会)  33 ( 1 ) 16 - 20 2015年01月

    総説・解説(学術雑誌), 単著

研究発表 【 表示 / 非表示

  • Cell Separation Column u sing Temperature Responsive Cationic Copolymer Modified Beads

    K. Nagase, D. Inanaga, G. Edatsune, Y. Nagata, A.M. Akimoto, H. Kanazawa

    Materials Research Meeting 2019 (MRM2019), 2019年12月, 口頭(一般)

  • 温度応答型アニオン性ポリマーブラシを用いた細胞分離の検討

    長瀬 健一, 内川 奈保, 廣谷 正, 秋元 文, 金澤 秀子

    第41回日本バイオマテリアル学会大会, 2019年11月, 口頭(一般), 日本バイオマテリアル学会

  • 細胞分離を目的とした温度応答性高分子の精密設計

    長瀬健一, 金澤秀子

    第68回高分子討論会, 2019年09月, 口頭(招待・特別)

  • 温度応答性ミックスモードカラムの開発と特性評価

    長瀬健一, 渡辺真梨亜, 善 文比古, 金澤秀子

    日本分析化学会 第68年会, 2019年09月, 口頭(一般)

  • 温度応答性カチオン交換型ミックスモードカラムの開発

    長瀬健一, 渡辺真梨亜, 善 文比古, 金澤秀子

    第32回バイオメディカル分析科学シンポジウム, 2019年08月, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 再生医療を革新的に効率化する機能性バイオ界面の創製

    2019年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 長瀬健一, 基盤研究(B) , 補助金,  代表

  • 酸素産生ナノ粒子を用いた革新的細胞組織移植法の確立

    2018年06月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 長瀬 健一, 挑戦的研究(萌芽), 補助金,  代表

  • mRNA送達による立体細胞組織内タンパク質発現を利用した脈管形成と血管新生誘導

    2018年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小林 純, 補助金,  分担

  • 細胞認識因子を組み込んだインテリジェント型細胞分離基材の開発

    2014年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 長瀬 健一, 基盤研究(C), 補助金,  代表

  • がん細胞シート工学による革新的3次元がん組織モデルの構築

    2013年04月
    -
    2016年03月

    中山正道, 基盤研究(B), その他,  分担

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受賞 【 表示 / 非表示

  • 日本分析化学会 関東支部 新世紀賞

    2019年01月

    受賞国: 日本

  • HPLC 2017 Jeju, Best Poster Award

    2017年11月

  • Best Young Investigator Poster Award, The 5th Asian Biomaterials Congress

    2015年05月

  • 日本バイオマテリアル学会 科学奨励賞

    2014年11月

    受賞国: 日本

  • IUMRS-ICA 2014 Young Scientist Awards BRONZE AWARDS

    2014年08月

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担当授業科目 【 表示 / 非表示

  • 課題研究(創薬物理化学)

    2019年度

  • 演習(創薬物理化学)

    2019年度

  • 卒業研究C

    2019年度

  • 卒業研究B

    2019年度

  • 卒業研究A

    2019年度

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