2026-02-19 ハーバード大学
<関連情報>
- https://seas.harvard.edu/news/cyborg-pancreas-organoids-reveal-how-cells-mature-and-synchronize
- https://www.science.org/doi/10.1126/science.aeb3295
埋め込まれたフレキシブル電子機器がヒト膵島細胞の電気的成熟の原理を明らかにする Implanted flexible electronics reveal principles of human islet cell electrical maturation
Qiang Li, Ren Liu, Zuwan Lin, Xinhe Zhang, […] , and Jia Liu
Science Published:19 Feb 2026
Editor’s summary
Pancreatic islets play a key role in the regulation of glucose homeostasis through the activities of α and β cells and their production of glucagon and insulin, respectively. Since the initial discovery of these hormones, we have become increasingly proficient at mimicking physiological patterns of glucose regulation by the administration of exogenous insulin, but much remains to be learned about the biology of the α and β cells themselves. Li et al. approached this problem by developing tiny stretchable electronics that can be implanted into stem cell–derived pancreatic organoids, monitoring the maturation of α and β cells in vitro (see the Perspective by Lang and Raoux). Using these electronics, the researchers were able to not only study the cells, but also influence their behavior, providing a valuable tool for further research and potentially also for therapeutic development. —Yevgeniya Nusinovich
Structured Abstract
INTRODUCTION
Human pluripotent stem cell–derived islets (SC-islets) hold promise for diabetes research and therapy but show functionally immature glucose responsiveness. Although several strategies promote maturation, SC-islets still fall short of the precision and dynamics of hormone secretion in primary islets. Whether this reflects poor coordination among α and β cells or intrinsic heterogeneity is unknown. Progress requires tools to decipher how individual cell functions specialize and synchronize within intact three-dimensional (3D) tissue over time.
RATIONALE
Recent advances in flexible, tissue-like nanoelectronics enable integration of stretchable electrodes into organoids during development, allowing long-term, noninvasive, single-cell electrophysiology, an opportunity not yet applied to SC-islet cells. We therefore integrated tissue-like, stretchable electronics into human pluripotent stem cell–derived pancreatic organoids to create “cyborg” pancreatic organoids, enabling months-long, single cell–resolved electrophysiology during pancreatic organoid maturation.
RESULTS
Cyborg pancreatic organoids enabled continuous recording of single-unit extracellular spiking activity within intact pancreatic organoids. Spike sorting isolated and clustered spikes to individual cells, allowing simultaneous capturing of single SC-α and -β cell electrical activities, distinguished by their characteristic responses to glucose. SC-α cells fired more rapid action potentials under low versus high glucose, which is consistent with glucagon secretion, whereas SC-β cells showed the opposite pattern, which is consistent with insulin release. Pharmacological perturbations further validated cell type–specific electrical behaviors. In situ electro-sequencing bridged these electrical signatures to transcriptionally defined SC-α and -β cells. Longitudinal tracking showed that SC-α and -β cells occupy either low or high basal firing electrical states and that increased organoid-level hormone responsiveness stems from increased electrical activity of SC-α and -β cells adopting both low and high basal firing states. Entrainment to daily metabolic cycles further demonstrated that circadian hormone secretion rhythms reflect synchronized oscillations in both SC-α and -β action potential firing rates and waveform profiles. Lastly, implanted electrical stimulators enabled electrical stimulation that selectively enhanced glucose-stimulated activity in SC-α and -β cells.
CONCLUSION
Cyborg pancreatic organoids provide a platform for continuous, single cell–resolved tracking of α and β cell electrical maturation within intact 3D tissue during maturation, uncovering mechanisms that enhance glucose responsiveness and cellular synchronization. This platform potentiates discovery of regulators of SC-islet maturation and provides a route toward engineering fully functional, tunable human islets, supporting future applications in disease modeling, drug discovery, and regenerative therapies for diabetes.
Cyborg pancreatic organoids.
(Left, top and bottom) Stretchable mesh nanoelectronics integrated with stem cell–derived pancreatic cells generated “cyborg” pancreatic organoids. Single-unit electrical activities from SC-α and -β cells were captured through spike sorting and linked to transcriptional identity through in situ electro-sequencing. Long-term recordings tracked cell-specific dynamics. Electrical stimulation enhanced glucose-dependent electrical responses. (Right, top and bottom) Entrainment to daily metabolic cycles coordinated circadian electrical-secretory rhythms that enhanced organoid activity in vitro.
Abstract
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.
