Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin

Abstract This study explored the impact of hydrolyzed gelatin (HG) concentration on the retention and therapeutic efficacy of human iPS cell-derived cardiomyocytes (hiPSC-CMs) when injected into the myocardium. The solubility of HG allows precise control over its concentration, influencing the distr...

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Main Authors: Jun Iida, Kazuki Kotani, Kozue Murata, Keisuke Hakamada, Wusiman Maihemuti, Yoshinobu Mandai, Yosuke Hiraoka, Kenji Minatoya, Hidetoshi Masumoto
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-87885-w
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author Jun Iida
Kazuki Kotani
Kozue Murata
Keisuke Hakamada
Wusiman Maihemuti
Yoshinobu Mandai
Yosuke Hiraoka
Kenji Minatoya
Hidetoshi Masumoto
author_facet Jun Iida
Kazuki Kotani
Kozue Murata
Keisuke Hakamada
Wusiman Maihemuti
Yoshinobu Mandai
Yosuke Hiraoka
Kenji Minatoya
Hidetoshi Masumoto
author_sort Jun Iida
collection DOAJ
description Abstract This study explored the impact of hydrolyzed gelatin (HG) concentration on the retention and therapeutic efficacy of human iPS cell-derived cardiomyocytes (hiPSC-CMs) when injected into the myocardium. The solubility of HG allows precise control over its concentration, influencing the distribution and leakage of injected solutions, which may affect therapeutic outcomes. Using both ex vivo and in vivo rat models, we investigated how varying HG concentrations affect the retention of solution and diffusion within the myocardium. In ex vivo static rat hearts, 10% HG minimized leakage but allowed significant diffusion. However, in pulsating in vivo hearts, 20% HG provided the best retention. In a rat myocardial infarction model, hiPSC-CMs suspended in 20% HG resulted in the highest cell retention. Echocardiogram showed a significant increase in the ejection fraction two weeks after transplantation compared to before transplantation. Additionally, cardiac magnetic resonance imaging (MRI) revealed that the ejection fraction was significantly higher than that of the sham group four weeks after transplantation. These findings suggest that optimizing HG concentration is crucial for enhancing the retention and therapeutic efficacy of hiPSC-CM transplants in treating heart disease.
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institution Kabale University
issn 2045-2322
language English
publishDate 2025-02-01
publisher Nature Portfolio
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series Scientific Reports
spelling doaj-art-13f389a25a0d4223b548544163a52a152025-02-09T12:31:55ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-87885-wRetention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatinJun Iida0Kazuki Kotani1Kozue Murata2Keisuke Hakamada3Wusiman Maihemuti4Yoshinobu Mandai5Yosuke Hiraoka6Kenji Minatoya7Hidetoshi Masumoto8Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics ResearchBiomedical Department, R&D Center, Nitta Gelatin IncClinical Translational Research Program, RIKEN Center for Biosystems Dynamics ResearchDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto UniversityClinical Translational Research Program, RIKEN Center for Biosystems Dynamics ResearchBiomedical Department, R&D Center, Nitta Gelatin IncBiomedical Department, R&D Center, Nitta Gelatin IncDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto UniversityClinical Translational Research Program, RIKEN Center for Biosystems Dynamics ResearchAbstract This study explored the impact of hydrolyzed gelatin (HG) concentration on the retention and therapeutic efficacy of human iPS cell-derived cardiomyocytes (hiPSC-CMs) when injected into the myocardium. The solubility of HG allows precise control over its concentration, influencing the distribution and leakage of injected solutions, which may affect therapeutic outcomes. Using both ex vivo and in vivo rat models, we investigated how varying HG concentrations affect the retention of solution and diffusion within the myocardium. In ex vivo static rat hearts, 10% HG minimized leakage but allowed significant diffusion. However, in pulsating in vivo hearts, 20% HG provided the best retention. In a rat myocardial infarction model, hiPSC-CMs suspended in 20% HG resulted in the highest cell retention. Echocardiogram showed a significant increase in the ejection fraction two weeks after transplantation compared to before transplantation. Additionally, cardiac magnetic resonance imaging (MRI) revealed that the ejection fraction was significantly higher than that of the sham group four weeks after transplantation. These findings suggest that optimizing HG concentration is crucial for enhancing the retention and therapeutic efficacy of hiPSC-CM transplants in treating heart disease.https://doi.org/10.1038/s41598-025-87885-w
spellingShingle Jun Iida
Kazuki Kotani
Kozue Murata
Keisuke Hakamada
Wusiman Maihemuti
Yoshinobu Mandai
Yosuke Hiraoka
Kenji Minatoya
Hidetoshi Masumoto
Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
Scientific Reports
title Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
title_full Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
title_fullStr Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
title_full_unstemmed Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
title_short Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin
title_sort retention of locally injected human ips cell derived cardiomyocytes into the myocardium using hydrolyzed gelatin
url https://doi.org/10.1038/s41598-025-87885-w
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