Sousonis V, Sfakianaki T, Ntalianis A, Nanas I, Kontogiannis C, Aravantinos D, Kapelios C, Katsaros L, Nana M, Sampaziotis D, et al. 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. J Cardiovasc Pharmacol TherJ Cardiovasc Pharmacol TherJ Cardiovasc Pharmacol Ther. 2021;26:88-99.
Abstract: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.
Notes:Sousonis, VasileiosSfakianaki, TitikaNtalianis, ArgiriosNanas, IoannisKontogiannis, ChristosAravantinos, DionysiosKapelios, ChrisKatsaros, LamprosNana, MariaSampaziotis, DimitriosSanoudou, DespinaPapalois, ApostolosMalliaras, KonstantinosengRandomized Controlled Trial, VeterinaryResearch Support, Non-U.S. Gov't2020/07/18 06:00J Cardiovasc Pharmacol Ther. 2021 Jan;26(1):88-99. doi: 10.1177/1074248420941672. Epub 2020 Jul 17.