Flexible nanoelectronics reveal arrhythmogenesis in transplanted human cardiomyocytes

• 成果类型: Article
• 署名作者: Aoyama, Junya; Liu, Ren; Zhang, Xinhe; Zhu, Anthony Y.; Luanpaisanon, Pichayathida; Velayutham, Nivedhitha; Garbern, Jessica C.; Cao, Fang; Barrera, Irving; Fandl, Hannah; Sokol, Morgan; Dasariraju, Satvik; Gil, Eun Seok; Aleksi, Elton; Amanuma, Toshi; Saucerman, Jeffrey J.; Chen, Fei; Liu, Jia; Lee, Richard T.
• 署名单位: Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Virginia (UVA) Health System; University of Virginia; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adw4612
• 发表日期: 2025-11-13
• 页码: eadw4612
• 关键词: cell-derived cardiomyocytes; SELF-ASSEMBLING PEPTIDE; cyclosporine-a; maturation; expression; rejection; rats

摘要

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.