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...

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Main Authors: Yuta Kurashina, Keisuke Fukada, Shun Itai, Shuichi Akizuki, Ryo Sato, Akari Masuda, Hidenori Tani, Jun Fujita, Keiichi Fukuda, Shugo Tohyama, Hiroaki Onoe
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202301831
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author Yuta Kurashina
Keisuke Fukada
Shun Itai
Shuichi Akizuki
Ryo Sato
Akari Masuda
Hidenori Tani
Jun Fujita
Keiichi Fukuda
Shugo Tohyama
Hiroaki Onoe
author_facet Yuta Kurashina
Keisuke Fukada
Shun Itai
Shuichi Akizuki
Ryo Sato
Akari Masuda
Hidenori Tani
Jun Fujita
Keiichi Fukuda
Shugo Tohyama
Hiroaki Onoe
author_sort Yuta Kurashina
collection DOAJ
description 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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spelling doaj.art-1d8a0aff19dc4f75a8977fef85d868482023-12-16T04:16:13ZengWileyAdvanced Science2198-38442023-12-011035n/an/a10.1002/advs.202301831Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force MeasurementYuta Kurashina0Keisuke Fukada1Shun Itai2Shuichi Akizuki3Ryo Sato4Akari Masuda5Hidenori Tani6Jun Fujita7Keiichi Fukuda8Shugo Tohyama9Hiroaki Onoe10Department of Mechanical Engineering Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanSchool of Integrated Design Engineering Graduate School of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanDepartment of Mechanical Engineering Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanDepartment of Mechanical and Systems Engineering, School of Engineering Chukyo University 101–2 Yagoto Honmachi, Showa‐ku Nagoya Aichi 466–8666 JapanSchool of Integrated Design Engineering Graduate School of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanSchool of Integrated Design Engineering Graduate School of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanDepartment of Cardiology Keio University School of Medicine 35 Shinanomachi Shinjuku‐ku Tokyo 160–8582 JapanDepartment of Cardiology Keio University School of Medicine 35 Shinanomachi Shinjuku‐ku Tokyo 160–8582 JapanDepartment of Cardiology Keio University School of Medicine 35 Shinanomachi Shinjuku‐ku Tokyo 160–8582 JapanDepartment of Cardiology Keio University School of Medicine 35 Shinanomachi Shinjuku‐ku Tokyo 160–8582 JapanDepartment of Mechanical Engineering Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama 223–8522 JapanAbstract 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.https://doi.org/10.1002/advs.202301831anchor‐freecontractile forceengineered heart microtissuehiPSC‐derived cardiomyocyteshydrogel
spellingShingle Yuta Kurashina
Keisuke Fukada
Shun Itai
Shuichi Akizuki
Ryo Sato
Akari Masuda
Hidenori Tani
Jun Fujita
Keiichi Fukuda
Shugo Tohyama
Hiroaki Onoe
Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
Advanced Science
anchor‐free
contractile force
engineered heart microtissue
hiPSC‐derived cardiomyocytes
hydrogel
title Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
title_full Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
title_fullStr Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
title_full_unstemmed Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
title_short Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement
title_sort hydrogel sheathed hipsc derived heart microtissue enables anchor free contractile force measurement
topic anchor‐free
contractile force
engineered heart microtissue
hiPSC‐derived cardiomyocytes
hydrogel
url https://doi.org/10.1002/advs.202301831
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