Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Sousonis Vasileios
Dissertation committee:
Δέσποινα Σανούδου, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ευστάθιος Ηλιοδρομίτης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεόδωρος Παπαϊωάννου, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σεραφείμ Νανάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αριστείδης Ηλιόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Παρίσης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεράσιμος Σιάσος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Ενδοστεφανιαία χορήγηση αλλογενών καρδιακών προγoνικών κυττάρων για τον περιορισμό της έκτασης του εμφράγματος του μυοκαρδίου
Translated title:
Intracoronary delivery of allogeneic cardiosphere-derived progenitor cells to reduce myocardial infarct size
Summary:
Background: Intracoronary delivery of allogenic cardiosphere derived cells (CDCs) during reperfusion of an acute myocardial infarction (AMI) has been proven safe and effective in preclinical studies. However, reperfusion injury and no-reflow phenomenon (NR) may adversely affect the distribution of CDCs within the myocardial area at risk (AR), limiting their efficacy. Intracoronary CDC delivery, on the other hand, can lead to exacerbation of NR due to cell microembolization. Aim: The aim of this study was to evaluate the intracoronary delivery of allogeneic CDCs during the acute phase of myocardial infarction, prior to significant NR development, in a porcine ischemia – reperfusion model. Methods: First, in a series of preliminary safety experiments, different doses of allogeneic CDCs were administered intracoronary, either 5 minutes before or 5 minutes after the onset of reperfusion (pre-rep and post-rep studies, respectively). No-reflow areas were measured in order to define the maximum safe cell dose for each delivery method. Second, cell delivery timing was chosen based on CDC retention within the AR. Finally, infarct size (IS) was evaluated in an efficacy study, 30 days after intracoronary CDC delivery. Results: Cell delivery was not associated with any arrhythmias or hemodynamic impairment. Five and ten million allogenic CDCs could be safely administered without deterioration of NR in the pre-rep and post-rep studies, respectively. Cell delivery prior to reperfusion resulted in increased CDC retention within the AR (7.7±8.2% vs 1.4±1.5% in the post-rep study), thus, in the efficacy study, 5 million CDCs were administered, 5 minutes prior to reperfusion. Treatment with allogeneic CDCs, in the efficacy study, was associated with reduced IS (37.4±9.9% of AR) compared to controls (49.9±7.4% of AR, p=0.03). Conclusions: Intracoronary delivery of 5 million allogeneic CDCs immediately prior to reperfusion onset is associated with satisfactory cell retention rates and leads to reduced infarct size without aggravation of microvascular obstruction. The proposed therapeutic approach could be applied to clinical practice during AMI reperfusion with primary percutaneous coronary intervention.
Main subject category:
Health Sciences
Keywords:
Myocardial infarction, cell therapy, cardiosphere-derived cells
Number of references:
133
