Extracellular electrophysiology on clonal human β-cell spheroids

Area of Science:

• Cellular Biology
• Endocrinology
• Biophysics

Background:

• Pancreatic islets are crucial for nutrient homeostasis.
• 3D cell-cell coupling in beta-cells is vital for physiological function.
• Extracellular electrophysiology using micro-electrode arrays (MEA) offers accessible monitoring of cell activity.

Purpose of the Study:

• To investigate if 3D spheroid formation enhances clonal beta-cell function.
• To assess electrical activity and hormone secretion in human and rodent beta-cell models.
• To evaluate spheroid models as alternatives to primary islets for electrophysiology.

Main Methods:

• Formation of 3D spheroids using hanging drop or proprietary devices.
• Extracellular electrophysiology recordings with multi-electrode arrays (MEA).
• Hormone secretion measurement via ELISA.

Main Results:

• Human EndoC-βH1 spheroids showed increased slow potentials (SP) frequency and amplitude compared to monolayers.
• Spheroids exhibited enhanced glucose-stimulated insulin secretion.
• Rodent INS-1 cells, when engineered for better cell-cell coupling, showed improved glucose responsiveness.

Conclusions:

• 3D spheroid formation significantly enhances the physiological function of human clonal beta-cell lines.
• These spheroid models serve as effective surrogates for primary islets in electrophysiology.
• The study highlights the utility of MEA for monitoring beta-cell function in 3D organoid models.