Flexible nanoelectronics reveal arrhythmogenesis in transplanted human cardiomyocytes.
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| Title: | Flexible nanoelectronics reveal arrhythmogenesis in transplanted human cardiomyocytes. |
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| Authors: | Aoyama, Junya (AUTHOR), Liu, Ren (AUTHOR), Zhang, Xinhe (AUTHOR), Zhu, Anthony Y. (AUTHOR), Luanpaisanon, Pichayathida (AUTHOR), Velayutham, Nivedhitha (AUTHOR), Garbern, Jessica C. (AUTHOR), Cao, Fang (AUTHOR), Barrera, Irving (AUTHOR), Fandl, Hannah (AUTHOR), Sokol, Morgan (AUTHOR), Dasariraju, Satvik (AUTHOR), Gil, Eun Seok (AUTHOR), Aleksi, Elton (AUTHOR), Amanuma, Toshi (AUTHOR), Saucerman, Jeffrey J. (AUTHOR), Chen, Fei (AUTHOR), Liu, Jia (AUTHOR), Lee, Richard T. (AUTHOR) |
| Source: | Science. 11/13/2025, Vol. 390 Issue 6774, p1-15. 15p. |
| Subjects: | Nanoelectronics, Arrhythmia, Neovascularization, Heart development, Stem cells, Electrophysiology, Heart failure, Extracellular matrix |
| Abstract: | The transplantation of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offers a potential treatment for heart failure, but arrhythmogenic automaticity can arise from these transplanted cells. In this study, we investigated the effects of RADA16, a clinically approved self-assembling peptide that forms nanofibers after injection, on the vascularization, myofibril structure, and electrophysiological adaptation of hiPSC-CMs transplanted into rat hearts. RADA16 accelerated the transition of hiPSC-CMs toward adultlike gene expression profiles, enhanced sarcomere organization, and improved vascularization in the transplanted site. Flexible mesh nanoelectronics revealed fibrillation of transplanted hiPSC-CMs within the beating recipient heart, and RADA16 drastically reduced the automaticity of hiPSC-CMs. Our findings demonstrate the potential of self-assembling nanofibers to advance cardiac cell therapy and how flexible mesh nanoelectronics technology could improve safety. Editor's summary: Cardiac injury can lead to complications such as heart failure, so a major goal of researchers in this field is to repair damaged myocardium. Unfortunately, transplantation of stem cell–derived cardiomyocytes into injured areas has not worked out well so far, and transplanted cells often cause potentially dangerous arrhythmias. To decrease this risk, Aoyama et al. combined human stem cell–derived cardiomyocytes with a self-assembling peptide that forms nanofibers, showing that the combination helps to improve the cells' maturation and function upon transplantation into rat hearts. The authors also designed flexible mesh nanoelectronics, which they used to monitor the electrical activity of the transplanted cells within the beating heart, providing a closer look at their function. —Yevgeniya Nusinovich INTRODUCTION: The transplantation of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offers transformative potential for heart failure therapy, but clinical translation is impeded by arrhythmogenic risk of transplanted cells. Immature hiPSC-CMs exhibit disorganized sarcomeres and poor electrical integration, increasing the risk of posttransplant arrhythmias. In this study, we investigated whether RADA16, a clinically approved hemostatic agent, can function as a bioactive scaffold to enhance the in vivo maturation, vascularization, and electrophysiological integration of transplanted hiPSC-CMs. RATIONALE: Self-assembling peptides (SAPs) can form nanofiber-based microenvironments that mimic the native extracellular matrix, and RADA16 in particular has established hemostatic properties. We hypothesized that RADA16 could enhance structural and functional integration of transplanted hiPSC-CMs by promoting sarcomeric maturation, facilitating host vessel anastomosis, and suppressing aberrant electrical activity. RESULTS: Using healthy rat hearts for transplantation studies, we evaluated the role for RADA16 in improving transplanted hiPSC-CM properties. After intramyocardial transplantation, hiPSC-CMs coinjected with RADA16 showed improvements in graft vascularization through host-derived vessels, compared with the hiPSC-CM Alone group. Spatiotemporal transcriptomics by Slide-seq also showed a shift toward enhanced cardiomyocyte maturation in transplanted cells, demonstrating that RADA16 supported myofibril maturation. SarcOmere Texture Analysis (SOTA) showed improvements in sarcomere organization and alignment in hiPSC-CMs coinjected with RADA16. Further, a flexible mesh nanoelectronics approach enabled real-time mapping of electrical activity within the graft site, revealing that RADA16 coinjection suppressed the arrhythmogenic automaticity of transplanted hiPSC-CMs. CONCLUSION: We show that transplantation of hiPSC-CMs with RADA16 improved cardiomyocyte maturational markers and graft vascularization in healthy rat hearts. Our flexible mesh nanoelectronics approach enabled evaluation of graft-host electrical coupling within the beating recipient rat heart, showing fibrillation in the hiPSC-CM Alone group but suppression of arrhythmogenesis in hiPSC-CMs coinjected with RADA16. Our results demonstrate the potential of SAPs such as RADA16 as clinically viable strategies to improve stem cell–derived cardiomyocyte transplantation to treat heart failure, and they also highlight the use of flexible mesh nanoelectronics technology to improve safety assessments. Flexible mesh nanoelectronics uncover arrhythmogenesis in hiPSC-CM grafts and its suppression by the self-assembling peptide RADA16.: Transplanted hiPSC-CMs alone exhibited poor myofibril gene maturation, disorganized sarcomeres, and arrhythmogenic activity. Coinjection with RADA16 enhanced cardiomyocyte gene expression profiles, promoted sarcomere organization, and supported graft vascularization, collectively mitigating arrhythmogenesis, as revealed by high-resolution mesh nanoelectronics analysis. [Illustration created using BioRender.com and Adobe Illustrator] [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | The transplantation of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offers a potential treatment for heart failure, but arrhythmogenic automaticity can arise from these transplanted cells. In this study, we investigated the effects of RADA16, a clinically approved self-assembling peptide that forms nanofibers after injection, on the vascularization, myofibril structure, and electrophysiological adaptation of hiPSC-CMs transplanted into rat hearts. RADA16 accelerated the transition of hiPSC-CMs toward adultlike gene expression profiles, enhanced sarcomere organization, and improved vascularization in the transplanted site. Flexible mesh nanoelectronics revealed fibrillation of transplanted hiPSC-CMs within the beating recipient heart, and RADA16 drastically reduced the automaticity of hiPSC-CMs. Our findings demonstrate the potential of self-assembling nanofibers to advance cardiac cell therapy and how flexible mesh nanoelectronics technology could improve safety. Editor's summary: Cardiac injury can lead to complications such as heart failure, so a major goal of researchers in this field is to repair damaged myocardium. Unfortunately, transplantation of stem cell–derived cardiomyocytes into injured areas has not worked out well so far, and transplanted cells often cause potentially dangerous arrhythmias. To decrease this risk, Aoyama et al. combined human stem cell–derived cardiomyocytes with a self-assembling peptide that forms nanofibers, showing that the combination helps to improve the cells' maturation and function upon transplantation into rat hearts. The authors also designed flexible mesh nanoelectronics, which they used to monitor the electrical activity of the transplanted cells within the beating heart, providing a closer look at their function. —Yevgeniya Nusinovich INTRODUCTION: The transplantation of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offers transformative potential for heart failure therapy, but clinical translation is impeded by arrhythmogenic risk of transplanted cells. Immature hiPSC-CMs exhibit disorganized sarcomeres and poor electrical integration, increasing the risk of posttransplant arrhythmias. In this study, we investigated whether RADA16, a clinically approved hemostatic agent, can function as a bioactive scaffold to enhance the in vivo maturation, vascularization, and electrophysiological integration of transplanted hiPSC-CMs. RATIONALE: Self-assembling peptides (SAPs) can form nanofiber-based microenvironments that mimic the native extracellular matrix, and RADA16 in particular has established hemostatic properties. We hypothesized that RADA16 could enhance structural and functional integration of transplanted hiPSC-CMs by promoting sarcomeric maturation, facilitating host vessel anastomosis, and suppressing aberrant electrical activity. RESULTS: Using healthy rat hearts for transplantation studies, we evaluated the role for RADA16 in improving transplanted hiPSC-CM properties. After intramyocardial transplantation, hiPSC-CMs coinjected with RADA16 showed improvements in graft vascularization through host-derived vessels, compared with the hiPSC-CM Alone group. Spatiotemporal transcriptomics by Slide-seq also showed a shift toward enhanced cardiomyocyte maturation in transplanted cells, demonstrating that RADA16 supported myofibril maturation. SarcOmere Texture Analysis (SOTA) showed improvements in sarcomere organization and alignment in hiPSC-CMs coinjected with RADA16. Further, a flexible mesh nanoelectronics approach enabled real-time mapping of electrical activity within the graft site, revealing that RADA16 coinjection suppressed the arrhythmogenic automaticity of transplanted hiPSC-CMs. CONCLUSION: We show that transplantation of hiPSC-CMs with RADA16 improved cardiomyocyte maturational markers and graft vascularization in healthy rat hearts. Our flexible mesh nanoelectronics approach enabled evaluation of graft-host electrical coupling within the beating recipient rat heart, showing fibrillation in the hiPSC-CM Alone group but suppression of arrhythmogenesis in hiPSC-CMs coinjected with RADA16. Our results demonstrate the potential of SAPs such as RADA16 as clinically viable strategies to improve stem cell–derived cardiomyocyte transplantation to treat heart failure, and they also highlight the use of flexible mesh nanoelectronics technology to improve safety assessments. Flexible mesh nanoelectronics uncover arrhythmogenesis in hiPSC-CM grafts and its suppression by the self-assembling peptide RADA16.: Transplanted hiPSC-CMs alone exhibited poor myofibril gene maturation, disorganized sarcomeres, and arrhythmogenic activity. Coinjection with RADA16 enhanced cardiomyocyte gene expression profiles, promoted sarcomere organization, and supported graft vascularization, collectively mitigating arrhythmogenesis, as revealed by high-resolution mesh nanoelectronics analysis. [Illustration created using BioRender.com and Adobe Illustrator] [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adw4612 |
