Investigating the immune response to somatic corneal stem cell allografts (360G-Wellcome-102804_Z_13_Z)

This project will examine the interaction between tissue specific stem cells and the immune system using the eye as a model. This is a critical aspect of cellular therapy about which little is known. Two populations of corneal stem cells will be used, LESC and CSSC. The specific objectives are: 1. To determine the immunological characteristics of LESC and CSSC in terms of their ability to activate or suppress T cell mediated immune responses. This will be achieved by detailed phenotypic anal yses of the stem cell populations together with in vitro functional immunological assays. 2. To create a mouse model of LSCD in which LESC and CSSC allograft rejection can be studied. 3. To demonstrate the mechanisms of allograft rejection following LESC and CSSC transplantation in the mouse model. 4. To investigate whether the immunomodulatory properties of CSSC can confer improved cell survival onto LESC allografts when both cell types are co-transplanted. 5. To determine whether co-trans plantation of LESC and CSSC from different allogeneic donors is a viable therapeutic option or whether co-transplantation requires a common allogeneic donor for both cell types. The findings will guide immunosuppressive regimes and strategies in corneal cell therapy.