Creating an immune-privileged site using retinal progenitor cells and biodegradable polymers.

Abstract

We describe the creation of local immune privilege (IP) using retinal progenitor cells (RPCs) and biodegradable polymers. Murine RPCs were seeded on poly(lactic-coglycolic acid) polymers to generate composite grafts. Composites or RPCs alone were transplanted into allogeneic kidney capsules. Grafts survived at all time points, differentiating into neurons and astrocytes. Upon treatment with interferon gamma (IFNgamma), major histocompatibility complex antigens were upregulated. Although 10% of IFNgamma-treated RPC grafts survived 14 days, 66% of the IFNgamma-treated composites survived in part by producing immune suppressive factors transforming growth factor-beta2, Fas ligand, and indoleamine 2,3-dioxygenase. The composites were assayed for delayed-type hypersensitivity (DTH) by seeding composites with antigen-presenting cells incubated with ovalbumin. This resulted in suppression of ovalbumin-specific DTH, indicating that composite grafts consisting of biodegradable polymers and central nervous system progenitor cells can be used to generate local IP. This technology may be used to promote the survival of nonprivileged grafts (e.g., pancreas, liver, or skin). Disclosure of potential conflicts of interest is found at the end of this article.