Reformed islets: a long-term primary cell platform for exploring mouse and human islet biology

Area of Science:

• Endocrinology
• Cell Biology
• Immunology

Background:

• Pancreatic islets are vital 3D micro-organs for maintaining beta-cell function via cell-cell and cell-matrix communication.
• Primary islets, the gold standard for in vitro studies, have limited culture viability (1-2 weeks).
• Existing in vitro models often lack immune cell components crucial for studying diabetes pathology.

Purpose of the Study:

• To develop a novel in vitro model using reformed pancreatic islets with extended culture life and preserved physiological characteristics.
• To enable high-resolution imaging and repeated functional assessments of beta-cells.
• To facilitate the study of beta-cell and immune cell interactions in diabetes models.

Main Methods:

• A novel protocol involving dispersion and reformation of pancreatic islets was developed.
• A fine-tuned culture environment was established for reformed islets.
• Analyses included assessment of composition, cytoarchitecture, insulin secretion, and transcriptional similarity to primary islets.

Main Results:

• Reformed islets exhibit physiological characteristics and cytoarchitecture similar to primary islets, including macrophages and T cells.
• Reformed islets retain insulin secretion capabilities in response to glucose.
• While showing partial dedifferentiation, reformed islets are transcriptionally similar to native islets and retain immune populations.

Conclusions:

• Reformed islets provide a valuable in vitro platform for studying diabetes pathology, offering extended culture viability and retaining key cellular components.
• This model allows for the investigation of interactions between beta-cells and immune cells, crucial for understanding T1DM and T2DM.
• Reformed islets offer advantages over current models by recapitulating complex cellular crosstalk and disease milieus.