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
| Autor: | Chris J. Kapelios, Argirios Ntalianis, Titika Sfakianaki, D. Aravantinos, Despina Sanoudou, Apostolos Papalois, Lampros Katsaros, Konstantinos Malliaras, Maria Nana, Vasileios Sousonis, Dimitrios Sampaziotis, Christos Kontogiannis, Ioannis Nanas |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Sus scrofa Myocardial Infarction Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Ventricular Function Left 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Transplantation Homologous Pharmacology (medical) Myocytes Cardiac Myocardial infarction Cells Cultured 030304 developmental biology Pharmacology 0303 health sciences Ventricular Remodeling business.industry Myocardium Infarct size medicine.disease Fibrosis Disease Models Animal Cardiology Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of cardiovascular pharmacology and therapeutics. 26(1) |
| ISSN: | 1940-4034 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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