The Sefton lab is exploring strategies to mitigate transplant rejection by the host immune system. These strategies include:
- Immune modulation – training the host immune system to accept the transplanted cells
- Immune isolation – physically separating transplanted cells from the host
The transplantation of non-self cells provokes a destructive immune response which attacks the transplanted, “invading,” cells. This immune response can be further exacerbated by inflammation associated with invasive transplantation procedures, and the nature of biomaterial-based transplantation vehicles. In order to mitigate these host responses, transplant recipients must be subjugated to a continuous immunosuppression regiment to prevent rejection. As a more friendly alternative, the Sefton lab is developing bioengineered tissue constructs which can incorporate the biologics necessary to locally promote transplant acceptance, without the need for chronic immunosuppressants. Immune mitigation include physical protection (1 – by microencapsulating cells within a semi-permeable protective polymer), biochemical protection (2 – through the immobilization of biologics on delivery vehicles), or the promotion of immune tolerance (3 – through the use of tolerogenic immune cells).
Current and future projects
- Optimization of microencapsulated islet transplantation as a therapy for type 1 diabetes
- Delivery of islets in biomaterials functionalized with immune-mitigating biologics
- Optimization of islet co-delivery with immune tolerizing cells (Tregs, tolerogenic DCs, etc.)