Cyborg islets: implanted flexible electronics reveal principles of human islet electrical maturation

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Electrophysiology

Background:

• Chronic electrophysiology studies require stable, long-term monitoring of tissue function.
• Understanding pancreatic islet maturation is key for developing effective diabetes treatments.
• Organogenesis of human stem cell-derived islets offers a model for studying islet development.

Purpose of the Study:

• To integrate stretchable electronics into human stem cell-derived pancreatic islets during organogenesis.
• To investigate single-cell electrophysiological maturation and stimulus-coupled dynamics over months.
• To uncover principles of electrical development for improving in vitro islet function.

Main Methods:

• Integration of tissue-like stretchable electronics during human stem cell-derived pancreatic islet organogenesis.
• Long-term (months) stable tracing of single-cell extracellular spike bursting dynamics.
• Adaptation of neural spike sorting methods to analyze electrophysiological patterns of alpha (SC-α) and beta (SC-β) like cells.

Main Results:

• Identified maturation-dependent electrical patterns and two distinct electrical states for SC-α and SC-β cells based on glucose thresholds.
• Observed that enhanced hormone stimulation capacity correlates with increased SC-α/β cells in low basal firing states, linked to metabolic gene upregulation.
• Demonstrated that circadian rhythms in hormone secretion reflect coordinated oscillations in cell-level electrical activity, suggesting a role in system-level responses.

Conclusions:

• Cyborg islets reveal principles of electrical maturation and cell-cell communication in pancreatic islets.
• Circadian rhythms play a role in coordinating system-level stimulus-coupled responses.
• Findings are vital for creating functional in vitro islets for research and therapeutic applications.