Echocardiography-guided percutaneous left ventricular intracavitary injection as a cell delivery approach in infarcted mice

Abstract

BackgroundIn the field of cell therapy for heart disease, a new paradigm of repeated dosing of cells has recently emerged. However, the lack of a repeatable cell delivery method in preclinical studies in rodents is a major obstacle to investigating this paradigm. Methods and ResultsWe have established and standardized a method of echocardiography-guided percutaneous left ventricular intracavitary injection (echo-guided LV injection) as a cell delivery approach in infarcted mice. Here, we describe the method in detail and address several important issues regarding it. First, by integrating anatomical and echocardiographic considerations, we have established strategies to determine a safe anatomical window for injection in infarcted mice. Second, we summarize our experience with this method (734 injections). The overall survival rate was 91.4%. Previous studies results suggest that 1x106 cells delivered via this method yielded similar retention in the heart at 24 h as 1x105 cells delivered via intracoronary or intramyocardial injection. Lastly, we examined the efficacy of this cell delivery approach. Compared with vehicle treatment, cardiac mesenchymal cells (CMCs) delivered via this method improved cardiac function assessed both echocardiographically and hemodynamically. Furthermore, repeated injections of CMCs via this method yielded greater cardiac function improvement than single dose administration. ConclusionEcho-guided LV injection is a feasible, reproducible, relatively less invasive and effective delivery method for cell therapy in heart disease. It is an important approach that could move the field of cell therapy forward, especially with regard to repeated cell administrations.