The field of cardiac regeneration using adult cardiac progenitor cells has the potential to revolutionize the treatment of heart failure. Preclinical studies in small and large animal models indicate that cardiac-derived progenitor cells (CDCs) can successfully regenerate myocardium in the setting of ischemic damage, but 2 main problems remain: low levels of CDC survival after transplantation (engraftment) and modest improvement in overall cardiac function. Using molecular imaging, we found 5 fold higher cell engraftment following injection of cells with fibrin glue suggesting that adhesion molecules play an important role in engraftment.The central hypothesis of this proposal is that early activation of integrin signaling (both, inside-out and outside-in) in CDCs would improve adhesion and cell survival, which would translate into increased in vivo engraftment and functional benefits. Here, we propose in vitro and invivo studies aimed at understanding the regulation of integrin-mediated signaling and its role in engraftment.
|Program type||Beginning Grant-in-Aid|
|Effective start/end date||07/01/2009 → 06/30/2011|