| Autor: |
Sousonis, Vasileios, Sfakianaki, Titika, Ntalianis, Argirios, Nanas, Ioannis, Kontogiannis, Christos, Aravantinos, Dionysios, Kapelios, Chris, Katsaros, Lampros, Nana, Maria, Sampaziotis, Dimitrios, Sanoudou, Despina, Papalois, Apostolos, Malliaras, Konstantinos |
| Předmět: |
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| Zdroj: |
Journal of Cardiovascular Pharmacology & Therapeutics; Jan2021, Vol. 26 Issue 1, p88-99, 12p |
| Abstrakt: |
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: Doseoptimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers longterm benefits. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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