CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

Abstract

Background: Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance. Methods: Human bone marrow derived CD271+ mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2−/− γc−/− mouse strain subjected to myocardial “infarction-reinfarction”. The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 min with a subsequent second permanent LAD ligation after seven days from the first infarct. Results: This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271+ MSC after the first MI significantly reduced VA induced after the second MI. Conclusions: In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271+ stem cells in vivo.