Endothelialized collagen based pseudo-islets enables tuneable subcutaneous diabetes therapy

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Transplantation Biology

Background:

• Pancreatic islets are vital for blood sugar regulation but are fragile and difficult to transplant.
• Islet transplantation is limited by poor survival due to hypoxia and nutrient diffusion issues post-transplant.
• Islet size and health significantly impact survival and function after transplantation.

Purpose of the Study:

• To engineer tuneable, size-controlled pseudo-islets for improved islet transplantation outcomes.
• To develop a novel scaffold-based approach for enhanced islet survival and vascularization.
• To assess the efficacy of engineered pseudo-islets in restoring normoglycemia in a diabetic mouse model.

Main Methods:

• De-aggregated pancreatic islets were dispersed within an endothelialized collagen scaffold to create size-controlled pseudo-islets.
• Subcutaneous transplantation of engineered pseudo-islets into streptozotocin-induced diabetic mice.
• Whole-implant imaging and tissue clearing techniques were used to analyze vascular architecture and cell proximity.

Main Results:

• Engineered pseudo-islets supported subcutaneous engraftment and successfully returned diabetic mice to normoglycemia.
• Pseudo-islets demonstrated regenerated vascular architecture post-transplantation.
• Insulin-secreting beta cells were located within 5 μm of a perfusable blood vessel, ensuring efficient nutrient supply.

Conclusions:

• This bottom-up islet engineering approach provides precise control over construct size and composition.
• The endothelialized scaffold facilitates critical revascularization, enhancing islet survival and function.
• This method offers a promising strategy for islet transplantation in the clinically relevant subcutaneous space.