Development of cardiovascular system using fundamental heart model and modelling of energy conversion mechanism

• Project/Area Number: 18H01338
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 18010:Mechanics of materials and materials-related
• Research Institution: Kyushu University
• Principal Investigator: Todo Mitsugu 九州大学, 応用力学研究所, 准教授 (80274538)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: iPS細胞 / 心筋細胞 / 拍動 / サルコメア力学 / 粘弾性 / 能動的応力 / 生体力学 / エネルギー変換 / 細胞工学 / 生体エネルギー / 粘弾性理論 / 数値解析 / 循環器系 / 生体材料

Outline of Final Research Achievements

Cardiac cell sheets with natural pulsation were successfully constructed using iPS cells derived cardiomyocytes as the basic material for the development of a fundamental heart model. A constitutive law to express the stress-strain response was derived from a theoretical model of active stress combined with a simple viscoelastic model. The constitutive model was found to coincide with the experimental result well.
A 3D tube structure was successfully developed using the cardiac cell sheets. It was then found that the internal fluid flow was connected with the pulsation behavior. It was also confirmed that the theoretical model of the constitutive law can be sued to predict the stress-strain response of the 3D tube model.

Academic Significance and Societal Importance of the Research Achievements

動物心筋細胞やiPS細胞由来心筋細胞を用いて自己的に拍動するアクチュエータを作製した研究例は見受けられるが、その力学挙動の詳細に関する研究は少なく、特に応力-ひずみ応答に関連した理論的研究はほとんど行われていなかった。本研究は、世界で初めてiPS細胞由来心筋細胞シートと３次元チューブ状構造体の拍動に関連した応力-ひずみ応答が、能動的応力の理論式と粘弾性モデルを組み合わせることで表現できることを明らかにした。さらに、本研究で開発したチューブ状構造体は、循環器系システムモデルの開発に利用可能であり、循環器系医学への貢献も期待される。

Research Products

• [Presentation] ヒトiPS細胞由来心筋細胞を用いたチューブ状構造体の作製と評価 (2021)
  • Author(s): 栗田寛子、東藤貢
  • Organizer: 第２０回日本再生医療学会総会
• [Presentation] 簡易エレクトロスピニング装置を用いた中空円筒状足場材の作製と評価 (2021)
  • Author(s): 東藤貢
  • Organizer: 日本バイオマテリアル学会2020年度九州ブロック講演会
• [Presentation] Mechanical analysis of pulsation behavior of human iPSC-derived cardiomyocites (2019)
  • Author(s): Hiroko Kurita, Saki Ikeda, Yasuyuki Morita, Mitsugu Todo
  • Organizer: International Conference on Advanced Technology in Experimental Mechanics 2019
  • Int'l Joint Research
• [Presentation] 心筋力学モデルを用いたヒトiPS細胞由来心筋細胞の拍動挙動の解析 (2019)
  • Author(s): 東藤貢、近藤聖奈、池田沙樹、栗田寛子
  • Organizer: 第18回日本再生医療学会総会