Implanted flexible electronics reveal principles of human islet cell electrical maturation
- Qiang Li
- Ren Liu
- Zuwan Lin
- Xinhe Zhang
- Wenbo Wang
- Israeli M. Galicia-Silva
- Mai Liu
- Zihan Gao
- Samuel D. Pollock
- Juan R. Alvarez-Dominguez
- Jia Liu
2026-02-19
Understanding how human pancreatic α and β cell electrical activities mature is critical for building fully functional stem cell–derived (SC-) pancreatic organoids for research and therapeutics. We implanted tissue-like, stretchable electronics during organogenesis of human pancreatic organoids, enabling months-long, single cell–resolved electrophysiology. Longitudinal single-cell tracking suggested that improved hormone responsiveness reflects increasing activity of SC-α and -β cells with low and high basal firing, linked to induction of energy and hormone metabolism genes. Daily metabolic entrainment showed that circadian hormone secretion rhythms reflect daily oscillation of SC-α and -β electrical characteristics, tied to induction of cell-cell communication and exocytic gene networks, revealing circadian coordination of cell-level, stimulus-coupled responses. Lastly, we showed that electrical stimulation, via implanted actuators, enhances SC-α and -β glucose responsiveness. Our results establish a bioelectronic framework to trace and modulate functional organoid maturation.