Junya Aoyama, Ren Liu, Xinhe Zhang, Anthony Zhu, Pichayathida Luanpaisanon, Nivedhitha Velayutham, Jessica C. Garbern, Fang Cao, Irving Barrera, Hannah Fandl, Morgan Sokol, Satvik Dasariraju, Eun Seok Gil, Elton Aleksi, Toshi Amanuma, Jeffrey J. Saucerman, Fei Chen, Jia Liu, Richard Lee
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.