Characterization of pattern recognition receptor responses against materials for cell encapsulation

Abstract

Islet transplantation has significant potential for the treatment of type I diabetes, but an immunoprotective barrier is necessary to protect the donor tissue from host rejection and to eliminate the need for systemic immunosuppressive therapy. Cell encapsulation is an attractive technology to enable donor cell transplantation, but clinical success has remained elusive due to immunological responses to the encapsulated materials. Alginate is the leading material for the microencapsulation of islet cells, successfully creating a barrier between the host immune system and implanted islet cells. However, inflammatory monocytes and macrophages initiate a cascade of immunological responses to the implanted materials, leading to a chronic inflammation that results in fibrosis of the implants and hypoxic death of the islet cells. These macrophages may sense alginate via pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and NOD-like receptors (NLRs). However, which PRRs are involved, how they recognize alginate, and whether alginate material characteristics and compositions can elicit different responses are not very well understood. To better understand the PRR mediated immune response to alginate, we devised an in vitro system to study the activation of PRRs against several commercially available alginates. Here, we report that alginate compositions and material characteristics can influence which PRRs activate and how strongly they can provoke PRR mediated immune response, and that direct cell-to-material contact is a crucial step in initiating such response.