Recent studies in mice have identified common thymic epithelial progenitor cells (TEPC) that were capable to re-establish a thymus in-vivo that fully supported thymopoiesis. These TEPC arise solely from endoderm progenitors during embryogenesis. We hypothesised that common TEPC may be generated in-vitro from embryonic stem (ES) cells that have differentiated towards definitive endoderm. It is our aim to develop methods for a controlled in-vitro differentiation of murine embryonic stem cells towards definitive ES cell-derived endoderm and subsequently towards common TEPC, that may further differentiate into mature, functional thymic tissue in-vivo after transplantation. Delineation of these conditions is aimed for in order to develop thymic regenerative cell therapy, which is considered pivotal in the development of allo-SCT. Recently, effective generation of definitive endoderm using a Sox-17 reporter ES celline was demonstrated. Currently, these endodermal cells are selected and further studied in-vivo upon transplantation in mice and in-vitro using different culture conditions.