Microphysiological Analysis Platform of Pancreatic Islet β-Cell Spheroids

Area of Science:

• Endocrinology
• Cell Biology
• Biomedical Engineering

Background:

• Diabetes mellitus is characterized by impaired insulin secretion and glucagon dysregulation.
• Understanding hormone release from pancreatic islets is crucial for diabetes research.
• Current models for measuring pancreatic beta-cell function lack robustness and reproducibility.

Purpose of the Study:

• To develop a microphysiological analysis platform (MAP) for uniform 3D pancreatic beta-cell spheroid formation.
• To enable large-scale morphological phenotyping and gene expression mapping under chronic glycemia and lipidemia.
• To investigate the mechanisms of beta-cell apoptosis in response to hyperglycemia and hyperlipidemia.

Main Methods:

• Scaffold-free formation of densely packed beta-cell spheroids in an array of 110 bioreactors.
• Utilizing a perfusion flow network mimicking a physiologically relevant microenvironment.
• Implementing dynamic perturbations to control glycemia and lipidemia, followed by apoptosis pathway analysis.

Main Results:

• The MAP successfully formed uniform 3D beta-cell spheroids.
• The platform allowed for precise control of glycemia and lipidemia.
• Apoptosis in beta-cell spheroids under hyperglycemia and hyperlipidemia was confirmed to be primarily mediated by reactive oxygen species and caspases.

Conclusions:

• The developed MAP provides a robust and reproducible model for studying pancreatic beta-cell function.
• This platform facilitates the investigation of chronic glycemia and lipidemia effects on beta-cells.
• The findings offer new insights into the pathophysiological mechanisms of beta-cell dysfunction in diabetes.