Abstract
Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 ± 2.88%) than that of naïve NPCCs and NPCCs in small capsule (86.83 ± 2.32%, 87.67 ± 2.07%, respectively) at day 7. The viability of naïve NPCCs decreased rapidly at day 14 (75.67 ± 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 ± 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 ± 0.09 and 2.13 ± 0.09) was conserved better compared to that of naïve NPCCs (2.04 ± 0.25 and 1.53 ± 0.32, respectively) and NPCCs in large capsules (2.04 ± 0.34 and 1.13 ± 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion.
Highlights
Diabetes mellitus type 1 is one of the most common endocrine diseases and is characterized by an absolute insulin deficiency
The viability of naïve neonatal pancreatic cell clusters (NPCC) decreased rapidly at day 14 (75.67 ± 1.75%), whereas the NPCCs encapsulated in small capsules maintained good viability (82.0 ± 2.19%) (Figure 3)
The insulin secretion of the islets encapsulated within calcium alginate microcapsules was investigated and compared with that of naïve islets by measuring the glucose-stimulated insulin secretion with 2.8 and 20 mM glucose (Figure 4)
Summary
Diabetes mellitus type 1 is one of the most common endocrine diseases and is characterized by an absolute insulin deficiency. The only replacement therapy to improve the metabolic control in diabetes mellitus patients other than conventional insulin therapy is the transplantation of insulin-producing cells, pancreatic islets or whole pancreas. Cell encapsulation strategies have been suggested as a solution to both the problems associated with immunosuppression and organ shortage problems. These technologies are based on the principle that foreign cells are protected against the host immune systems, including antibodies and cytotoxic cells, by sequestering them within an artificial membrane. Major challenges are stilled encountered, such as decreased metabolites, O2 transfer associated with the thick membrane of large capsules (>700 μm) and total volume of microencapsulated islet used for transplantation. The need exists to develop islet encapsulation strategies that minimize transplant volume and maximize metabolite transfer
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