(646d) Improving Cellular Function of Microencapsulated Cells Using An Improved Alginate Formulation

Cell encapsulation is a powerful in vivo technique for isolating cells and other particles from the host immune system for implantation applications. Numerous different materials and cell types have been investigated in the past decade, but cell encapsulation is not widely used in the clinic due to poor oxygen and nutrient transport through the capsule compared to vascularized tissue. Many patients with autoimmune diseases such as type 1 diabetes (T1D) are poised to benefit from microencapsulation of cells which reintroduce a lost functionality. The Edmonton Protocol has shown the possibilities and promise of human islet transplantation for the treatment of diabetes, while illuminating key hurdles to making this treatment a reality. Our laboratory explores challenges in encapsulating pancreatic islets of Langerhans for the treatment of T1D, with the goal of improving current methods and formulations while maintaining and enhancing islet functionality.

In T1D, a patient's immune system attacks the functioning islets, causing an inability to respond to high blood glucose levels. A current challenge with islet transplantation is creating an immuno-isolated environment to protect the transplanted cells from attack by the host immune system. Diffusion limitations between the patient's blood stream and the transplanted islets pose another challenge. An islet is a cluster of many cell types, averaging about 150µm in diameter, with the insulin producing beta cells located in the center of the islet, making them the most susceptible to transport limitations. Hypoxic conditions pose a major threat to islet functionality and insulin secretion.

Previous work by islet experts has shown that culturing explanted islets with perfluorodecalin, a perfluorocarbon (PFC), enhances islet viability and functionality in culture. For transplantation purposes, islets must be encapsulated to avoid a lifetime of immunosuppressants for the patient. Our study incorporates both an immuno-isolated environment in the form of an alginate capsule and improved islet function using a PFC/alginate formulation. Both islet function and capsule stability are monitored over multiple weeks, suggesting formulations for both promoting bead structure and insulin secretion. Methods for separating islet-containing capsules from empty capsules have been established as well as characterization of capsule size distribution and structural homogeneity from different encapsulation techniques.