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Multiscale design platform for innovating freezing processes of iPS cells

Research Project

Project/Area Number 20K21102
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 27:Chemical engineering and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Sugiyama Hirokazu  東京大学, 大学院工学系研究科(工学部), 教授 (70701340)

Co-Investigator(Kenkyū-buntansha) 紀ノ岡 正博  大阪大学, 大学院工学研究科, 教授 (40234314)
Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsプロセス設計 / 凍結保護剤 / ハイブリッドモデリング / 多目的最適化 / 費用対効果 / CFD / 計算科学 / ヒトiPS細胞 / 凍結 / 解凍 / モデル化 / シミュレーション / 計算化学 / ライフサイクルアセスメント / iPS細胞 / 保護剤 / 環境影響評価 / 凍結プロセス / 最適化
Outline of Research at the Start

iPS細胞のプライチェーンでは保存や輸送のための凍結が繰り返されるが、最適なプロセスは未確立である。本研究の目的は、iPS細胞凍結の課題を分子・細胞・プロセスの各スケールで解決し、さらに成果を階層的につなげることで、単独のスケールでは成し得ない革新を起こす「マルチスケール設計基盤」を構築することである。

Outline of Final Research Achievements

The objective of this research is to solve the problem of iPS cell freezing at the molecular, cellular, process, and societal scales, and to establish a multi-scale design framework that connects these scales. At each scale, we developed methods for cryoprotectant screening, freezing process design and scale-up, and cost-benefit analysis for manufacturing. Furthermore, we identified the connecting variables and information linking each scale, and proposed a multiscale design framework. In this study, the principal investigator and the co-investigator conducted modeling and simulation studies and experimental studies, respectively, and proceeded with the research while integrating the results.

Academic Significance and Societal Importance of the Research Achievements

iPS細胞が実生産されると、サプライチェーンで凍結が繰り返し実施されることが想定される。しかしiPS細胞はアポトーシスの進行しない-150℃まで冷却される過程で、脱水や氷晶形成によりダメージを受ける。実生産に向けたスケールアップも未達成であり、モデル化やシミュレーション、最適化の技術を取り入れた、化学工学的検討が求められていた。本研究の成果は、これらの社会的ニーズに応えつつ、新しい化学工学の萌芽につながるものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results) Presentation (16 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results)

  • [Journal Article] A CFD model-based design of seeding processes for two-dimensional mesenchymal stem cell cultivation2023

    • Author(s)
      Scholz Benedikt X., Hayashi Yusuke, Udugama Isuru A., Kino-oka Masahiro, Sugiyama Hirokazu
    • Journal Title

      Computers & Chemical Engineering

      Volume: 171 Pages: 108157-108157

    • DOI

      10.1016/j.compchemeng.2023.108157

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A screening support method of cryoprotective agents for regenerative medical products considering environmental impacts2023

    • Author(s)
      Hayashi Yusuke, Shigeyama Akinori, Sugiyama Hirokazu
    • Journal Title

      Chemical Engineering Research and Design

      Volume: 191 Pages: 83-92

    • DOI

      10.1016/j.cherd.2023.01.021

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A multilayered approach to scale-up forced convection-based freezing of human induced pluripotent stem cells2022

    • Author(s)
      Scholz Benedikt X., Hayashi Yusuke, Udugama Isuru A., Kino-oka Masahiro, Sugiyama Hirokazu
    • Journal Title

      Computers & Chemical Engineering

      Volume: 163 Pages: 107851-107851

    • DOI

      10.1016/j.compchemeng.2022.107851

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 生産性と品質を考慮したヒトiPS細胞向け充填・凍結・解凍プロセスのハイブリッドモデルベースと設計2022

    • Author(s)
      林 勇佑, 杉山 弘和
    • Journal Title

      Pharm Tech Japan

      Volume: 38 Pages: 585-588

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Hybrid-model-based design of fill-freeze-thaw processes for human induced pluripotent stem cells considering productivity and quality2022

    • Author(s)
      Hayashi Yusuke、Kino-oka Masahiro、Sugiyama Hirokazu
    • Journal Title

      Computers and Chemical Engineering

      Volume: 156 Pages: 107566-107566

    • DOI

      10.1016/j.compchemeng.2021.107566

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cost-effectiveness analysis in the manufacture of allogeneic human induced pluripotent cells in Japan by agent-based modeling2022

    • Author(s)
      Hayashi Yusuke、Oishi Kota、Sugiyama Hirokazu
    • Journal Title

      Chemical Engineering Research and Design

      Volume: 182 Pages: 172-182

    • DOI

      10.1016/j.cherd.2022.03.038

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharma PSE Spotlight 第14回:生産性と品質を考慮したヒトiPS細胞向け充填・凍結・解凍プロセスのハイブリッドモデルベースと設計2022

    • Author(s)
      林 勇佑、杉山 弘和
    • Journal Title

      Pharm Tech Japan

      Volume: 38 Pages: 585-588

    • Related Report
      2021 Research-status Report
  • [Journal Article] Model-based assessment of temperature profiles in slow freezing for human induced pluripotent stem cells2021

    • Author(s)
      Hayashi Yusuke, Horiguchi Ikki, Kino-oka Masahiro, Sugiyama Hirokazu
    • Journal Title

      Computers & Chemical Engineering

      Volume: 144 Pages: 107150-107150

    • DOI

      10.1016/j.compchemeng.2020.107150

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Computational screening of cryoprotective agents for regenerative medical products using quantum chemistry and molecular dynamics simulations2021

    • Author(s)
      Hayashi Yusuke, Nakajima Yuka, Sugiyama Hirokazu
    • Journal Title

      Cryobiology

      Volume: in press Pages: 101-109

    • DOI

      10.1016/j.cryobiol.2021.03.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharma PSE Spotlight 第13回:ヒトiPS細胞の緩慢凍結プロセスにおける冷却温度プロファイルのモデルベースト評価2021

    • Author(s)
      林 勇佑, 杉山 弘和
    • Journal Title

      Pharm Tech Japan

      Volume: 37 Pages: 255-259

    • Related Report
      2020 Research-status Report
  • [Journal Article] Multiobjective Dynamic Optimization of Slow Freezing Processes for Human Induced Pluripotent Stem Cells by Modeling Intracontainer Condition2020

    • Author(s)
      Hayashi Yusuke, Horiguchi Ikki, Kino-oka Masahiro, Sugiyama Hirokazu
    • Journal Title

      Computer Aided Chemical Engineering

      Volume: 48 Pages: 265-270

    • DOI

      10.1016/b978-0-12-823377-1.50045-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] CFDシミュレーションを用いたヒトiPS細胞の連続凍結プロセス設計2023

    • Author(s)
      林 勇佑, Scholz Benedikt, 杉山 弘和
    • Organizer
      化学工学会 第88年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Role of physical, statistical, and hybrid modelling approaches for pharmaceutical manufacturing2022

    • Author(s)
      Hirokazu Sugiyama
    • Organizer
      10th Asian Symposium on Process Systems Engineering
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A hybrid-model-based approach to continuous freezing process design for human induced pluripotent stem cells2022

    • Author(s)
      Yusuke Hayashi, Hirokazu Sugiyama
    • Organizer
      10th Asian Symposium on Process Systems Engineering
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An agent-based model for cost-effectiveness analysis in the manufacture of allogeneic human induced pluripotent cells in Japan2022

    • Author(s)
      Yusuke Hayashi, Kota Oishi, Hirokazu Sugiyama
    • Organizer
      The 14th International Symposium on Process Systems Engineering
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hirokazu Sugiyama2022

    • Author(s)
      Pharma PSE: a multiscale approach for reimagining pharmaceutical manufacturing
    • Organizer
      The 14th International Symposium on Process Systems Engineering
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトiPS細胞に対する連続凍結プロセスの適用2022

    • Author(s)
      林 勇佑, 杉山 弘和
    • Organizer
      第65回 自動制御連合講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒトiPS細胞凍結プロセスにおけるトンネルフリーザーの適用2022

    • Author(s)
      林 勇佑, 杉山 弘和
    • Organizer
      化学工学会 第53回秋季大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Pharma PSE:医薬品製造を"reimagine"するマルチスケール・アプローチ2022

    • Author(s)
      杉山 弘和
    • Organizer
      2022年 ISPE日本本部 年次大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞向け凍結保存プロセスのマルチスケール設計2022

    • Author(s)
      林 勇佑、杉山 弘和
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Research-status Report
  • [Presentation] ハイブリッドモデルを用いたヒトiPS細胞の充填・凍結・解凍プロセス設計2021

    • Author(s)
      林 勇佑、紀ノ岡 正博、杉山 弘和
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Research-status Report
  • [Presentation] エージェントベーストモデルを用いた他家iPS細胞治療の費用対効果分析2021

    • Author(s)
      林 勇佑, 大石 宏太, 杉山 弘和
    • Organizer
      化学工学会第86年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 数値流体力学シミュレーションを用いたヒトiPS細胞緩慢凍結プロセスのスケールアップ検討2021

    • Author(s)
      林 勇佑, Scholz Benedikt, 杉山 弘和
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Model-Based Assessment of Freezing Temperature Profiles for Human Induced Pluripotent Stem Cells2021

    • Author(s)
      Yusuke Hayashi, Ikki Horiguchi, Masahiro Kino-Oka, Hirokazu Sugiyama
    • Organizer
      2020 AIChE Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Quantum chemistry and molecular dynamics simulations on cryoprotective agents for human stem cells2020

    • Author(s)
      Yusuke Hayashi, Yuka Nakajima, Hirokazu Sugiyama
    • Organizer
      The 9th Asian Symposium on Process Systems Engineering (9th PSE Asia)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞の緩慢凍結における温度プロファイルの最適化シミュレーション2020

    • Author(s)
      林 勇佑, 堀口 一樹, 紀ノ岡 正博, 杉山 弘和
    • Organizer
      化学工学会 第51回秋季大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Multiobjective dynamic optimization of slow freezing processes for human induced pluripotent stem cells by modeling intracontainer condition2020

    • Author(s)
      Yusuke Hayashi, Ikki Horiguchi, Masahiro Kino-Oka, Hirokazu Sugiyama
    • Organizer
      The 30th European Symposium on Computer-Aided Process Engineering (ESCAPE-30)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-08-03   Modified: 2024-01-30  

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