Kanazawa, Hideko



Faculty of Pharmacy, Department of Pharmaceutical Sciences 創薬物理化学講座 (Shiba-Kyoritsu)



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Research Areas 【 Display / hide

  • Physical pharmacy

Research Keywords 【 Display / hide

  • Functional Polymer, HPLC, DDS


Books 【 Display / hide

  • 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, 2018.12

    Scope: 温度応答性クロマトグラフィー

  • ゲルテクノロジーハンドブック、第1篇第3章第3節 機能性ナノ界面を用いた温度応答性クロマトグラフィー

    KANAZAWA Hideko, NTS, 2014.10

    Scope: 80-87

  • わかりやすい薬剤学計算問題の解き方

    KANAZAWA Hideko, 改訂版ネオメディカル, 2014

  • 製剤化のサイエンス

    KANAZAWA Hideko, 第6版ネオメディカル, 2014

  • 図解製剤学

    KANAZAWA Hideko, 南山堂, 2013.04

    Scope: 20-62

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Papers 【 Display / hide

  • 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   110565 2020.01

    ISSN  09277765

     View Summary

    © 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.

  • Characteristic differences of cell sheets composed of mesenchymal stem cells with different tissue origins

    Nakao M., Inanaga D., Nagase K., Kanazawa H.

    Regenerative Therapy (Regenerative Therapy)  11   34 - 40 2019.12

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    © 2019 The Japanese Society for Regenerative Medicine Introduction: Stem cell therapy with mesenchymal stem cells (MSCs)has been widely used in many clinical trials, and therapy with MSC sheets shows promise for patients. However, there are few reports characterizing MSC sheets. In the present study, the properties of MSC sheets derived from bone marrow, adipose tissue, and umbilical cord were evaluated. Methods: Cell sheets were fabricated with MSCs from different tissue origins in temperature-responsive cell culture dishes with and without pre-coating of fetal bovine serum (FBS). MSC adhesion behavior in the culture dish was observed. Secretion of cytokines related to cell proliferation and immune regulation from MSC sheets was investigated by ELISA. The adhesion properties of the MSC sheets were investigated by time-lapse microscopy. Results: Different cell adhesion and proliferation rates in temperature-responsive cell culture dishes were observed among the three types of MSCs. FBS pre-coating of the dishes enhanced cell attachment and proliferation in all cell types. Harvested cell sheets showed high attachment capacity to tissue culture polystyrene dish surfaces. Conclusions: MSC sheets can be fabricated from MSCs from different tissue origins using temperature-responsive cell culture dishes. The fabricated MSC sheets could be useful in cell transplantation therapies by choosing appropriate types of MSCs that secrete therapeutic cytokines for the targeted diseases.

  • 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 DW, Kanazawa H, Okano T

    Stem cell research & therapy (Stem Cell Research and Therapy)  10 ( 1 ) 353 2019.11

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    © 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 2019.06

    ISSN  09277765

     View Summary

    © 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.

  • Adsorption-Desorption Control of Fibronectin in Real Time at the Liquid/Polymer Interface on a Quartz Crystal Microbalance by Thermoresponsivity

    Li J., Kaku T., Tokura Y., Matsukawa K., Homma K., Nishimoto T., Hiruta Y., Akimoto A., Nagase K., Kanazawa H., Shiratori S.

    Biomacromolecules (Biomacromolecules)  20 ( 4 ) 1748 - 1755 2019.04

    ISSN  15257797

     View Summary

    Copyright © 2019 American Chemical Society. The cell manipulation technique using thermoresponsive polymers is currently attracting much attention for applications in the medical field. To achieve arbitrary and accurate cell control, it is necessary to intensely research fibronectin behavior. A smart surface, which has thermoresponsive wettability and which can adsorb or desorb fibronectin repeatedly without the presence of cells, was fabricated by an electrospinning method. The fabricated coating changed its structure as the temperature was changed, and this transformation could substitute for the pulling force generated by the cytoskeletal contraction of cells. Moreover, a coated quartz crystal microbalance was able to detect the fibronectin behavior as frequency shifts, which could be used in the estimation of the mass shift with the aid of suitable equations. This coating and measurement system can contribute greatly not only to the development in the medical field centered on biomaterial manipulation technologies, but also to the improvement of medical instruments.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 細胞導入を制御可能な刺激応答性高分子を用いたナノキャリアの開発

    山之内 翔, 勝山 直哉, 蛭田 勇樹, 綾野 絵理, 金澤 秀子

    高分子論文集 75 ( 2 ) 116 - 127 2918.03

    Introduction and explanation (scientific journal), Joint Work

  • 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 2019.07

    Introduction and explanation (scientific journal), Joint Work,  ISSN  0913-5006

  • 効果的ながん治療を目指したCD44ターゲティングナノキャリア

    山之内 翔, 金澤 秀子

    Drug Delivery System (じほう)  34 ( 1 ) 38 - 45 2019.01

    Introduction and explanation (scientific journal), Joint Work,  ISSN  09135006

  • Comparison of plasma propofol concentration for apnea, response to mechanical ventilation, and airway device between endotracheal tube and supraglottic airway device in beagles

    Iizuka T., Masui K., Kanazawa H., Nishimura R.

    Journal of Veterinary Medical Science (Journal of Veterinary Medical Science)  80 ( 9 ) 1420 - 1423 2018.09

    ISSN  09167250

     View Summary

    © 2018 The Japanese Society of Veterinary Science. The relationships between propofol plasma concentrations and the pharmacodynamic endpoints may differ according to a type of airway device. To clarify these relationships in different airway devices would be useful to avoid the complication such as apnea and intraoperative awareness. The aim of this study was to investigate the influence of difference of airway device on propofol requirement during maintenance of anesthesia in dogs. We compared the influence of airway devices on the plasma propofol concentrations for apnea, response to mechanical ventilation, and response to airway device between endotracheal tube (ETT) and supraglottic airway device (SGAD) in Beagles. The pharmacodynamic effects were repeatedly assessed at varying propofol concentrations. The plasma concentrations (mean ± SD) of propofol in the ETT and SGAD groups were 10.2 ± 1.8 and 10.9 ± 2.4 µg/ml for apnea (P=0.438), 7.9 ± 1.2 and 7.4 ± 1.5 µg/ml for response to mechanical ventilation (P=0.268), and 5.2 ± 0.7 and 5.4 ± 1.5 µg/ml for response to airway device (P=0.580), respectively. Required propofol concentration during maintenance of anesthesia may be similar between ETT and SGAD. Without moderate to strong stimuli such as airway device insertion or painful stimulation during surgery, the type of airway device may have little impact on required propofol concentration during maintenance of anesthesia in dogs.

  • 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 2018.04

    Introduction and explanation (scientific journal), Joint Work

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Presentations 【 Display / hide

  • 抗酸化物質封入経皮吸収型リポソーム製剤の機能性評価

    寺内 麻緒莉, 中谷 友惟香, 豊田 晴香, 柿崎 友里, 永田 佳子, 金澤 秀子

    第31回ビタミンE研究会 (愛媛) , 2020.01, Poster (general)

  • 温度応答性クロマトグラフィ―を用いたオリゴヌクレオチド分析法の検討

    山崎 開智, 前川 祐太朗, 長瀬 健一, 金澤 秀子

    第30回クロマトグラフィー科学会議 (京都) , 2019.12, Poster (general)

  • 温度応答性スピンカラムを用いた水系溶媒のみによる除タンパク法の開発

    石澤 佑太, 長瀬 健一, 金澤 秀子

    第30回クロマトグラフィー科学会議 (京都) , 2019.12, Poster (general)

  • 正電荷を有する温度応答性高分子ブラシ修飾シリカビーズを用いた幹細胞分離カラムの開発

    枝常 吾郎, 山田 創太, 長瀬 健一, 金澤 秀子

    第30回クロマトグラフィー科学会議 (京都) , 2019.12, Poster (general)

  • 温度変化により温和な抗体精製を可能にするHPLCカラムの開発

    石井 咲樹, 山田 創太, 長瀬 健一, 金澤 秀子

    第30回クロマトグラフィー科学会議 (京都) , 2019.12, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 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


    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(B), Co-investigator

  • 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


    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), Co-investigator

  • Development of high performance separation and purification technology for cell therapy and biopharmaceuticals


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金澤 秀子, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • 疾患バイオマーカー探索のための機能的RNA-タンパク複合体分離精製法の構築


    文部科学省・日本学術振興会, 科学研究費助成事業, 金澤秀子, 基盤研究(B), Principal Investigator

  • 生体内動態の時空間制御による機能的核酸デリバリーシステムの創製


    文部科学省・日本学術振興会, 科学研究費助成事業, 金澤秀子, 挑戦的萌芽研究, Principal Investigator

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Awards 【 Display / hide

  • 日本分析化学会 学会賞

    金澤 秀子, 2017.09, 日本分析化学会, 温度応答性クロマトグラフィーを用いた分離・分析システムの創製とその応用

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 日本

  • クロマトグラフィー科学会学会賞

    金澤秀子., 2008.12, クロマトグラフィー科学会, 機能性高分子を用いた温度制御型新規分離システムの開発.

  • HPLC 2005 Best Poster Paper Award First Prize.

    Hideko Kanazawa, 2005.07, 29th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2005)

    Type of Award: International Academic Awards

  • 日本分析化学会関東支部新世紀賞

    金澤秀子., 2002.03, 日本分析化学会関東支部

    Type of Award: Awards of National Conference, Council and Symposium

  • 生命科学啓明賞

    金澤秀子., 2002.03, 財団法人 啓明会

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

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Courses Taught 【 Display / hide











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