Dissertation committee:
Σεραφείμ Νανάς, Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
Αντώνης Μανώλης,Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
Ιωάννης Παρίσης,Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
Στυλιανός Ορφανός,Καθηγτής,Ιατρική Σχολή,ΕΚΠΑ
Χριστίνα Ρούτση,Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Βασιλειάδης,Επίκουρος Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
Νικολέττα Ροβίνα,Επίκουρη Καθηγήτρια,Ιατρική Σχολή,ΕΚΠΑ
Summary:
Background: Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The “no-reflow” phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell delivery in areas of microvascular obstruction (MVO). We hypothesized that CDC-induced cardioprotection would be enhanced by cell administration prior to reperfusion, when microvasculature is still relatively intact, to facilitate widespread cell delivery within the ischemic area.
Methods and Results: We studied 18 farm pigs; 12 completed the specified protocol. We performed a randomized, placebo-controlled study to assess the long-term efficacy of intracoronary infusion of 5 million allogeneic CDCs, delivered at 5 minutes prior to reperfusion, in a porcine model of acute myocardial infarction (AMI). The CDC therapy resulted in decreased scar size, improved regional systolic function, and attenuation of adverse cardiac remodeling (manifested as preserved global systolic function, preserved end-systolic volume, and decreased interstitial fibrosis) compared to placebo at 30 days post-MI.
Conclusions: Dose - optimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers long term
benefits.