Modeling embryonic heart vascular plexus development and sympathetic innervation on a human heart organoid

processes. Assembly of these vascularized EMOs with human iPSC-derived sympathetic neuron spheroids yields innervated EMOs exhibiting integrated neurovascular organization and functional responses to nicotine stimulation (iV-EMOs). This modular, developmentally guided organoid system features coordinated human cardiac, vascular, and neural development, providing a physiologically relevant platform for studying heart morphogenesis, neurovascular interactions, and regenerative therapeutic strategies.