Hydrogel-Sheathed hiPSC-Derived Heart Microtissue Enables Anchor-Free Contractile Force Measurement

Yuta Kurashina; Keisuke Fukada; Shun Itai; Shuichi Akizuki; Ryo Sato; Akari Masuda; Hidenori Tani; Jun Fujita; Keiichi Fukuda; Shugo Tohyama; Hiroaki Onoe

doi:10.1002/advs.202301831

Hydrogel-Sheathed hiPSC-Derived Heart Microtissue Enables Anchor-Free Contractile Force Measurement

Yuta Kurashina, Keisuke Fukada, Shun Itai, Shuichi Akizuki, Ryo Sato, Akari Masuda, Hidenori Tani, Jun Fujita, Keiichi Fukuda, Shugo Tohyama, Hiroaki Onoe

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-term culture. This paper proposes a hydrogel-sheathed human induced pluripotent stem cell (hiPSC)-derived heart microtissue (H³M) that can provide an anchor-free contractile force measurement platform in commonly used multi-well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H³M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.

Original language	English
Article number	2301831
Journal	Advanced Science
Volume	10
Issue number	35
DOIs	https://doi.org/10.1002/advs.202301831
Publication status	Published - 15-12-2023
Externally published	Yes

All Science Journal Classification (ASJC) codes

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

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10.1002/advs.202301831

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title = "Hydrogel-Sheathed hiPSC-Derived Heart Microtissue Enables Anchor-Free Contractile Force Measurement",

abstract = "In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-term culture. This paper proposes a hydrogel-sheathed human induced pluripotent stem cell (hiPSC)-derived heart microtissue (H3M) that can provide an anchor-free contractile force measurement platform in commonly used multi-well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H3M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.",

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author = "Yuta Kurashina and Keisuke Fukada and Shun Itai and Shuichi Akizuki and Ryo Sato and Akari Masuda and Hidenori Tani and Jun Fujita and Keiichi Fukuda and Shugo Tohyama and Hiroaki Onoe",

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AU - Kurashina, Yuta

AU - Fukada, Keisuke

AU - Itai, Shun

AU - Akizuki, Shuichi

AU - Sato, Ryo

AU - Masuda, Akari

AU - Tani, Hidenori

AU - Fujita, Jun

AU - Fukuda, Keiichi

AU - Tohyama, Shugo

AU - Onoe, Hiroaki

PY - 2023/12/15

Y1 - 2023/12/15

N2 - In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-term culture. This paper proposes a hydrogel-sheathed human induced pluripotent stem cell (hiPSC)-derived heart microtissue (H3M) that can provide an anchor-free contractile force measurement platform in commonly used multi-well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H3M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.

AB - In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-term culture. This paper proposes a hydrogel-sheathed human induced pluripotent stem cell (hiPSC)-derived heart microtissue (H3M) that can provide an anchor-free contractile force measurement platform in commonly used multi-well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H3M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.

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KW - hiPSC-derived cardiomyocytes

KW - hydrogel

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Hydrogel-Sheathed hiPSC-Derived Heart Microtissue Enables Anchor-Free Contractile Force Measurement

Abstract

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