In summary, the study demonstrates that a short course of costimulation-adhesion blockade treatment is sufficient to induce engraftment of xenogeneically transplanted hESC derivatives in both injured and healthy tissues, and to promote cardiac protection. Application of hESC and iPSC-derived cells holds great promise for cell replacement therapies in man, with clinical trials already ongoing in USA/Europe. This study represents an important step forward in overcoming the immunologic barriers that have continued to hamper the full realization of highly promising pluripotent stem cell-based therapies41, and that must be addressed before their eventual clinical application. It was surprising to see that traditional immunosuppressive therapies used to prevent solid organ rejection, such as calcineurin inhibitors and corticosteroids, are insufficient to prevent human embryonic stem cell rejection following transplantation. We were able to demonstrate that a short-course, dualagent regimen that prevents optimal T cell activation is sufficient to promote the robust and long-term survival of embryonic stem cell derivatives in both healthy and injured tissues in mouse models. The superior response of the transplanted cells to the costimulation-adhesion therapy may be attributed to its repression of both adaptive and innate immunity, which is likely to aid in mitigating the tissues’ rejection of these characteristically immunogenic cells. This led to both local and systemic upregulation of T cell immunoglobulin and mucin domain 3 (TIM3), a Th-1-specific cell surface protein, in addition to an overall reduction of pro-inflammatory cytokines. The results of this study published in STEM CELLS 2013 were featured on Stanford SCOPE (http://scopeblog.stanford.edu/2013/08/19/shushing-t-cells-promotes-acceptance-of-stem-celltherapies-say-stanford-researchers/) and other news outlets (http://www.prweb.com/releases/2013/8/prweb11033138.htm).