Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs With Acute Myocardial Infarction Reduces Infarct Size and Attenuates Adverse Cardiac Remodeling
δείτε την πρωτότυπη σελίδα τεκμηρίου στον ιστότοπο του αποθετηρίου του φορέα για περισσότερες πληροφορίες και για να δείτε όλα τα ψηφιακά αρχεία του τεκμηρίου*
Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells
Immediately Prior to Reperfusion in Pigs With Acute Myocardial
Infarction Reduces Infarct Size and Attenuates Adverse Cardiac
Remodeling
Sousonis, Vasileios
Sfakianaki, Titika
Ntalianis, Argirios and
Nanas, Ioannis
Kontogiannis, Christos
Aravantinos, Dionysios and
Kapelios, Chris
Katsaros, Lampros
Nana, Maria
Sampaziotis,
Dimitrios
Sanoudou, Despina
Papalois, Apostolos
Malliaras,
Konstantinos
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 81 farm pigs; 55 completed the specified
protocols. A dose-optimization study in infarcted pigs demonstrated that
the doses of 5 million and 10 million CDCs are the maximum safe doses
that can be administered intracoronarily at 5 minutes prior to and at 5
minutes post-reperfusion, respectively, without aggravating MVO.
Quantification of acute cell retention by polymerase chain reaction
demonstrated that cell delivery prior to reperfusion resulted in higher
cardiac cell retention compared to delivery post-reperfusion. We then
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 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.
(EN)
*Η εύρυθμη και αδιάλειπτη λειτουργία των διαδικτυακών διευθύνσεων των συλλογών (ψηφιακό αρχείο, καρτέλα τεκμηρίου στο αποθετήριο) είναι αποκλειστική ευθύνη των αντίστοιχων Φορέων περιεχομένου.
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