Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment
Summary: Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessme...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422400213X |
| _version_ | 1797328635482341376 |
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| author | Junjun Li Ying Hua Yuting Liu Xiang Qu Jingbo Zhang Masako Ishida Noriko Yoshida Akiko Tabata Hayato Miyoshi Mikio Shiba Shuichiro Higo Nagako Sougawa Maki Takeda Takuji Kawamura Ryohei Matsuura Daisuke Okuzaki Toshihiko Toyofuku Yoshiki Sawa Li Liu Shigeru Miyagawa |
| author_facet | Junjun Li Ying Hua Yuting Liu Xiang Qu Jingbo Zhang Masako Ishida Noriko Yoshida Akiko Tabata Hayato Miyoshi Mikio Shiba Shuichiro Higo Nagako Sougawa Maki Takeda Takuji Kawamura Ryohei Matsuura Daisuke Okuzaki Toshihiko Toyofuku Yoshiki Sawa Li Liu Shigeru Miyagawa |
| author_sort | Junjun Li |
| collection | DOAJ |
| description | Summary: Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine—two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications. |
| first_indexed | 2024-03-08T06:54:32Z |
| format | Article |
| id | doaj.art-fe04cb70067b4e8287a8e0e8e4148976 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T06:54:32Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fe04cb70067b4e8287a8e0e8e41489762024-02-03T06:39:08ZengElsevieriScience2589-00422024-02-01272108992Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessmentJunjun Li0Ying Hua1Yuting Liu2Xiang Qu3Jingbo Zhang4Masako Ishida5Noriko Yoshida6Akiko Tabata7Hayato Miyoshi8Mikio Shiba9Shuichiro Higo10Nagako Sougawa11Maki Takeda12Takuji Kawamura13Ryohei Matsuura14Daisuke Okuzaki15Toshihiko Toyofuku16Yoshiki Sawa17Li Liu18Shigeru Miyagawa19Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanFujifilm Corporation, Ashigarakami 258-8577, Kanagawa, JapanCardiovascular Division, Osaka Police Hospital, Tennoji 543-0035, Osaka, JapanDepartment of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan; Department of Medical Therapeutics for Heart Failure, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Physiology, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata 573-1121, Osaka, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Research Center, Osaka University, Osaka, Japan; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Immunology and Molecular Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, JapanDepartment of Future Medicine, Division of Health Science, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Corresponding authorDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Corresponding authorDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Corresponding authorSummary: Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine—two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications.http://www.sciencedirect.com/science/article/pii/S258900422400213XBioengineeringBiotechnologyCardiovascular medicineStem cells research |
| spellingShingle | Junjun Li Ying Hua Yuting Liu Xiang Qu Jingbo Zhang Masako Ishida Noriko Yoshida Akiko Tabata Hayato Miyoshi Mikio Shiba Shuichiro Higo Nagako Sougawa Maki Takeda Takuji Kawamura Ryohei Matsuura Daisuke Okuzaki Toshihiko Toyofuku Yoshiki Sawa Li Liu Shigeru Miyagawa Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment iScience Bioengineering Biotechnology Cardiovascular medicine Stem cells research |
| title | Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment |
| title_full | Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment |
| title_fullStr | Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment |
| title_full_unstemmed | Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment |
| title_short | Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment |
| title_sort | human induced pluripotent stem cell derived closed loop cardiac tissue for drug assessment |
| topic | Bioengineering Biotechnology Cardiovascular medicine Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S258900422400213X |
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