The effects of cell density and device arrangement on the behavior of macroencapsulated beta-cells.

Over the last several decades, considerable research has focused on the development of cell encapsulation technology to treat a number of diseases, especially type 1 diabetes. One of the key advantages of cell encapsulation is that it permits the use of xenogenic tissue, particularly animal-derived cell lines. This is an attractive idea, because it circumvents the issue of a limited human organ supply. Furthermore, as opposed to whole islets, cell lines have a better proliferative capacity and can easily be amplified in culture to provide an endless supply of uniform cells. We have previously described a macroencapsulation device for the immunoisolation of insulin-secreting 1-cells. The aim of this work was to optimize the viability and insulin secretion of cells encapsulated within this device. Specifically, the effects of cell packing density and device membrane configuration were investigated. The results indicated that cell density plays an important role in the secretory capacity of the cells, with higher cell density leading to increased insulin secretion. Increasing the transport area of the capsule by modifying the membrane configuration also led to an improvement in the insulin output of the device.

Biocompatibility of nanoporous alumina membranes for immunoisolation.

Cellular immunoisolation using semi-permeable barriers has been investigated over the past several decades as a promising treatment approach for diseases such as Parkinson's, Alzheimer's, and Type 1 diabetes. Typically, polymeric membranes are used for immunoisolation applications; however, recent advances in technology have led to the development of more robust membranes that are able to more completely meet the requirements for a successful immunoisolation device, including well controlled pore size, chemical and mechanical stability, nonbiodegradability, and biocompatibility with both the graft tissue as well as the host. It has been shown previously that nanoporous alumina biocapsules can act effectively as immunoisolation devices, and support the viability and functionality of encapsulated beta cells. The aim of this investigation was to assess the biocompatibility of the material with host tissue. The cytotoxicity of the capsule, as well as its ability to activate complement and inflammation was studied. Further, the effects of poly(ethylene glycol) (PEG) modification on the tissue response to implanted capsules were studied. Our results have shown that the device is nontoxic and does not induce significant complement activation. Further, in vivo work has demonstrated that implantation of these capsules into the peritoneal cavity of rats induces a transient inflammatory response, and that PEG is useful in minimizing the host response to the material.

Nanoporous alumina capsules for cellular macroencapsulation: transport and biocompatibility.

BACKGROUND: Currently, the most widely used treatment for diabetes is the daily subcutaneous injection of recombinant human insulin. Daily injections, however, cannot match the physiological biphasic behavior of normal insulin release, nor can they precisely meet the demands of food intake, exercise, and stress. Cellular encapsulation, or immunoisolation, is a possible solution to this problem. This cell-based therapy allows patients to receive the benefits of more physiological insulin and blood glucose regulation, without the need for immunosuppressants that are associated with organ or cell transplantation. METHODS: Immunoisolation capsules were fabricated out of aluminum and aluminum oxide using a two-step anodization procedure. The diffusion behavior of glucose, immunoglobulin G (IgG), and insulin were measured. Furthermore, the functionality and viability of encapsulated MIN6 cells were tested. Finally, live cells were stained and imaged using confocal microscopy. RESULTS: Data indicated that this device is effective in allowing the transport of relevant molecules such as glucose and insulin, while at the same time significantly impeding the transport of IgG, suggesting that it would be efficacious in protecting cell grafts in vivo. Furthermore, encapsulated cells were able to respond dynamically to glucose input signals. Finally, cell staining showed that the viability of encapsulated cells is maintained after 24 h, although the cells appear to be more heavily concentrated at the area that is closest to the membrane. CONCLUSIONS: This study has shown that nanoporous alumina membranes, with well-controlled pore sizes, can be used for the encapsulation of therapeutic cells and may provide an alternative encapsulation strategy for the treatment of diabetes.