Immune Modulation Potential of ESC Extracts on T Cells

Abstract

Embryonic stem cells (ESCs) possess hypo-immunogenic properties and have the capacity to modulate allogeneic immune response. ESCs have been shown to reduce immune activation in response to third party antigen presenting cells (APCs) in vitro and have the capacity to promote allograft survival in vivo. Clinical use of live ESCs to treat immunological disorders, however, risks teratoma or ectopic tissue formation. Accordingly, the way lab is studying the immune modulatory potentials of ESC-derived factors and recently, found that dendritic cells (DCs) treated with human ESC extracts are poor stimulators of purified allogeneic T cells compared to those DCs treated with vehicle or fibroblast extracts. In the present study, I found that ESC-derived extracts directly inhibit T cell proliferation and suppress their activation without inducing cell death. Furthermore, ESC extracts are able to suppress Th1 polarization while increasing the numbers of Foxp3+ CD4+ CD25+ regulatory T cells. Moreover, I found that a protein called Milk fat globule-EGF factor 8 (MFG-E8) appears to be highly expressed in ESCs. Importantly, neutralizing MFG-E8 substantially abrogated the immune suppressive effects of ESC extracts on T cell activation. These findings lead to future studies to further define specific immunomodulatory factors derived from ESCs for potential applications.