Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device

Area of Science:

• Biomedical Engineering
• Cell Biology
• Diabetes Research

Background:

• Encapsulation of pancreatic islets is a key strategy for type 1 diabetes treatment, aiming to create an immune-isolated environment for transplanted beta cells.
• Islet endothelial cell damage during isolation compromises beta cell function and insulin secretion, highlighting the need to preserve cell-cell interactions.
• Endothelial cells produce crucial factors that influence beta cell insulin secretion, underscoring the importance of mutual signaling in functional encapsulation systems.

Purpose of the Study:

• To investigate the impact of co-culturing beta cells with endothelial cells on beta cell function within encapsulation devices.
• To determine if combining beta cells and endothelial cells in composite aggregates enhances insulin secretion compared to beta cells alone.

Main Methods:

• Mouse insulinoma MIN6 cells and human umbilical vein endothelial cells were used to form composite aggregates on an agarose microwell platform.
• These composite aggregates were encapsulated in flat poly(ether sulfone)/polyvinylpyrrolidone devices.
• Functionality was assessed via glucose-induced insulin secretion tests and compared to non-encapsulated free-floating aggregates.

Main Results:

• Composite aggregates (80-100 µm diameter) closely mimicked native pancreatic islets.
• Co-cultured aggregates demonstrated improved glucose-stimulated insulin secretion compared to MIN6 cell-only aggregates.
• Encapsulated composite aggregates exhibited higher insulin secretion than encapsulated MIN6 cell-only aggregates.

Conclusions:

• Co-culture of MIN6 cells with human umbilical vein endothelial cells significantly enhances insulin secretion within encapsulation devices.
• The interaction between beta cells and endothelial cells is critical for developing functional pancreatic islet encapsulation systems for diabetes therapy.