Advances in islet encapsulation technologies

Abstract

Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans.

Figure 1 ∣. Islet and β-cell transplantation systems.

a ∣ Schematic of the ViaCyte device, which is a rechargeable encapsulating system about half the size of a business card in which the membrane functions to contain the cells and to limit the access of immune cells, but allows the transport of nutrients from the exterior of the device and hormones from the encapsulated cells. Patients would be implanted with 4–6 units. b ∣ Image and schematic of the Beta-O₂ device demonstrating the ports for recharging oxygen and the encapsulation device. The schematic illustrates the central module that can be charged with oxygen to diffuse outwards to the islets contained within a membrane. The device is approximately 2.5 inches in diameter. The membrane allows for nutrient and hormone transport but is impregnated with alginate to restrict cell infiltration. c ∣ Islet microencapsulation with alginate hydrogels. This image shows genetically engineered pig islets entrapped within alginate hydrogels. d ∣ Host response to the transplantation of encapsulated islets. Transplantation of the capsules leads to a host response that will depend on multiple factors (for example, cells, materials, transplant site and so on). Shortly after transplantation into tissues (left-hand side), the host response to transplantation and the material can consist of an inflammatory response (pink region) with nearby blood vessels. Over time, the inflammatory response would ideally resolve without fibrosis and would allow for vascular growth adjacent to the capsule for nutrient and hormone exchange. However, shed antigens released from the islet may contribute to immune cell recruitment and activation. PTFE, polytetrafluoroethylene.