Alginate Microencapsulation Enhances Islet Function by Protecting against IL-1β

Background: Islet transplantation is a potential therapeutic avenue for type 1 diabetes mellitus. However, the lack of an effective vehicle for transplantation poses a challenge in sustaining long-term islet viability and shielding from immune rejection in vivo. Alginate encapsulation can be a promising strategy to optimize the microenvironment of transplanted cells. The most utilized form is sodium alginate for its natural biocompatibility. We hypothesize encapsulation of islets within alginate can enhance their viability and protect against detrimental effects of Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine known to impair islet viability and function. Methods: Pancreatic islets were purchased from Prodo Laboratories, Inc. (Aliso Viejo, CA). Islets were encapsulated in alginate utilizing a custom 3D-printed droplet generator and cured with barium chloride (10 mM BaCl). Microencapsulated islets were cultured in PRODO media supplemented with IL-1β (50 pmol/L). After 48 hours, viability was assessed utilizing Calcein AM and Ethidium homodimer-1 staining. Furthermore, islet function was evaluated using Glucose Stimulated Insulin Secretion (GSIS). ELISA was used to detect c-peptide production and glucagon release and islet viability was quantified using ImageJ. Results: Non-encapsulated islets demonstrated a significant increase in c-peptide production in the presence of IL-1β (p < 0.01; Figure 1A). On the other hand, microencapsulated islets demonstrated an increase in c-peptide production. A similar response was observed with glucagon release for non-encapsulated (p < 0.01; Figure 1B) and microencapsulated islets treated with IL-1β. There was no significant change in viability for encapsulated and non-encapsulated islets exposed to IL-1β. Conclusion: Encapsulation of pancreatic islets appears to protect islets from pro-inflammatory stress, thereby preserving their functionality. This microencapsulation holds potential for enhancing islet transplantation and longevity of islets invivo. While encapsulated islets exhibit comparable viability to non-encapsulated islets, their function is improved when treated with IL-1 β. Funding: Private Foundation Support