Stem cell therapy holds great promise in the treatment of cardiac disease. A major limitation to the efficacy of cell therapy is the poor viability of the transplanted cells. Our present studies revealed that genetic modification of MSCs effectively protects transplanted MSCs against ischemia and increases cell survival after implantation. Continued development and application of genetic manipulation approaches in stem cells will undoubtedly lead to more efficient guidance and control of stem cell fate and improved stem cell function.