Introduction:

Micro-encapsulation of islets for the treatment of Type I diabetes has shown limited efficacy in small-scale clinical trials. The lack of success may be related to the transplantation site, encapsulation material, or formation of pericapsular fibrotic overgrowth. Our collaborators have shown that encapsulated rat islets at macro diameters (1.5 mm) are better at curing diabetic C57b/6 mice when compared to micro diameters (0.5 mm), largely due to decreased fibrosis of macro beads (Veiseh et al, Nature Materials 2015). In this study, we investigated the ability of macro-encapsulated cynomolgus monkey islets to cure diabetes using immune incompetent and competent mouse models.

Methods:

Cyno islets were encapsulated in 1.5 mm high G alginate gelled with a 20 mM barium chloride solution. These were transplanted into streptozotocin (STZ) induced diabetic mice using a marginal amount of islets (1,500 islets/1 ml beads/mouse). Blood glucose levels were measured and an oral glucose tolerance test (OGTT) was performed. In vitro functionality assays were performed including viability, dithizone staining, glucose stimulated insulin secretion (GSIS), and a dynamic multi-parametric perifusion assay to measure insulin secretion and intracellular responses to challenges.

Results/Conclusion:

Macro-encapsulated islets cured STZ nude mice (n=9) similarly to kidney capsule transplanted islets (n=5) (cure rates: 77% vs. 75%). Furthermore, macro-encapsulated cyno islets exhibited consistent glycemic control for at least 6 months in a STZ C57b/6 mouse model (n=8). Immediately following encapsulation, islets were aliquotted into mouse doses and transplanted into STZ nude mice on day 1 and 14 post-encapsulation (n=8 per group). Results indicate that short-term culture does not impact in vivo islet graft function (30 day cure rate: 88% vs. 86%); (OGTT, p = 0.43). This suggests that islet masses can be protected during short-term culture within macro-beads, which may prove beneficial for patient safety in the future to allow for a complete analysis of quality control assessments prior to transplantation.

CITATION INFORMATION: Bochenek M, McGarrigle J, Mendoza-Elias J, Marchese E, Nourmohammadzadeh M, Wang Y, Khan A, Omami M, Yeh C.-C, Lacik I, Strand B, Oberholzer J. In Vivo and In Vitro Characterization of 1.5 mm Ba²⁺-Alginate Macro-Encapsulated Cynomolgus Monkey Islets. Am J Transplant. 2016;16 (suppl 3).

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