Cell encapsulation within semi-permeable devices represents a local immunoisolation strategy for cell-based therapies without the need for systemic immunosuppression. The encapsulation system allows for the diffusion of nutrients into the device which are important for cell survival, and the therapeutic payload produced by the cells to diffuse out in order to regulate the disease of choice. The barrier provided by the semi-permeable membrane prevents the entrance of immune cells that would otherwise destroy the therapeutic cells. For some time, encapsulation strategies have been applied to insulin producing islets of Langerhans transplantation and have shown long-term diabetes correction in many rodent models. However, these same strategies have failed when applied to a small number of clinical trials with diabetic patients. The foreign body response (FBR) to the biomaterials comprising the devices has been the major issue when testing in larger animal models. FBR results in the deposition of a dense ECM and cellular network covering the devices that restricts nutrition of the cells inside and compromises viability. Our lab is developing novel biomaterials and drug delivery strategies that can resist the foreign body response and fibrosis of implantable materials. Without fibrosis covering these encapsulation devices, free nutritional exchange for the therapeutic cells inside ensures continued secretion of their therapeutic payload for regulation of the disease of interest. This talk will discuss the discovery of a number of immune modulatory materials that have been developed in the Anderson/Langer lab that can reduce fibrotic activation and can lead to the protection of allogeneic islets in non-human primates for up to 4 months without any immune suppression.
1. What is the major contributor to the failure of immunoisolated cell therapy devices in patients
2. Identify key immune cell types for immunomodulatory biomaterials