Implanted flexible electronics reveal principles of human islet cell electrical maturation

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Endocrinology

Background:

• Functional stem cell-derived (SC-) pancreatic organoids are crucial for diabetes research and therapeutics.
• Understanding the maturation of human pancreatic alpha and beta cell electrical activity is key to developing these organoids.

Purpose of the Study:

• To establish a bioelectronic framework for tracing and modulating the functional maturation of human pancreatic organoids.
• To investigate the electrical activity and metabolic entrainment of SC-α and -β cells during organoid development.

Main Methods:

• Implantation of tissue-like, stretchable electronics during human pancreatic organoid organogenesis.
• Longitudinal, single cell-resolved electrophysiology and single-cell tracking.
• Daily metabolic entrainment and electrical stimulation via implanted actuators.

Main Results:

• Improved hormone responsiveness in SC-α and -β cells correlates with increased electrical activity and gene expression related to metabolism.
• Circadian rhythms in hormone secretion are linked to daily oscillations in SC-α and -β cell electrical characteristics and gene networks.
• Electrical stimulation enhances SC-α and -β cell glucose responsiveness.

Conclusions:

• The developed bioelectronic framework enables detailed monitoring of organoid maturation.
• This approach provides insights into the electrical and metabolic development of pancreatic cells within organoids.
• The study demonstrates a method to actively enhance the functional maturation of stem cell-derived pancreatic organoids.