Human skin-derived precursor cells are poorly immunogenic and modulate the allogeneic immune response.

摘要

Human skin-derived precursors (hSKP) are multipotent somatic stem cells that persist within the dermis throughout adulthood and harbor potential clinical applicability. In the present study we investigated their immunogenicity and immunosuppressive features, both in vitro and in vivo. As such, this study provides a solid basis for developing their future clinical applications. We found that hSKP express HLA-ABC molecules, but not HLA-DR, rendering them poorly immunogenic. Using a co-culture set-up, we could further demonstrate that hSKP inhibit the proliferation of allogeneic activated T-cells and alter their cytokine secretion profile, in a dose-dependent manner. Co-transplantation of hSKP and human PBL into SCID mice also showed a significant impairment of the graft-versus-host response one week post transplantation and a drastic increase in survival time of 60%. From a mechanistic point of view, we found that hSKP require cell contact as well as secretion of soluble inhibitory factors in order to modulate the immune response. The expression/secretion levels of these factors further increases upon inflammation or in the presence of activated T-cells. As such, we believe that these features could be beneficial in a later allogeneic clinical setting, because rejection of engrafted allogeneic hSKP might be delayed or even avoided due to their own promotion of a tolerogenic micro-environment. Stem Cells 2014.