Mending a broken heart: can gene modulation bolster therapeutic performance of adult stem cells?

Myocardial infarction and the congestive heart failure (HF) that follows are poised to be the leading cause of death in the modern world. Although advances in technology and patient management have helped reduce the mortality rate, the ability to sustain long-term recovery of the heart post-infarction is nearly impossible. This is mainly due to the inability of the adult heart to repair the infarcted region as it has limited regenerative capacity. The implementation of adult stem cells (ASCs) for cardiac therapy has been associated with improvements in cardiac function in several preclinical HF models, however, their effectiveness in the clinical setting has been inconsistent with several large clinical trials reporting disappointing outcomes. To enhance the effectiveness of ASCs, the incorporation of transgenes that bolster their homing and engraftment, anti-apoptotic, anti-inflammation, and pro-angiogenic properties has been proposed and in support, recent findings show transgenic ASCs to be more effective than their naïve counterpart by attenuating disease progression and improving cardiac recovery. Moreover, in addition to improving the therapeutic performance of ASCs, gene modulation provides insight on the fundamental mechanisms underlying the effectiveness of the respective therapy. Here, we review the current status on ASC therapy for cardiac repair and discuss the implementation of transgenic ASCs for restoring the failing heart and improving clinical outcomes.