Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain.

The concept of using an immunoisolation device to facilitate the transplantation of islets without the need for immunosuppression has been around for more than 50 yr. Significant progress has been made in developing suitable materials that satisfy the need for biocompatibility, durability, and permselectivity. However, the search is ongoing for a device that allows sufficient oxygen transfer while maintaining a barrier to immune cells and preventing rejection of the transplanted tissue. Separating the islets from the rich blood supply in the native pancreas takes its toll. The immunoisolated islets commonly suffer from hypoxia and necrosis, which in turn triggers a host immune response. Efforts have been made to improve the supply of nutrients by using proangiogenic factors to augment the development of a vascular supply in the transplant site, by using small islet cell aggregates to reduce the barrier to diffusion of oxygen, or by creating scaffolds that are in close proximity to a vascular network such as the omental blood supply. Even if these efforts are successful, the shortage of donor islet tissue available for transplantation remains a major problem. To this end, a search for a renewable source of insulin-producing cells is ongoing; whether these will come from adult or embryonic stem cells or xenogeneic sources remains to be seen. Herein we will review the above issues and chart the progress made with various immunoisolation devices in small and large animal models and the small number of clinical trials carried out to date.

Microfabrication of homogenous, asymmetric cell-laden hydrogel capsules.

Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the material/surface properties associated with efficient encapsulation were identified. Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucose-responsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process.