Abstract 11076: Visualization of Cardiac Uptake of Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles After Intramyocardial or Intravenous Injection in Murine Myocardial Infarction

Abstract

Introduction: In animal models, human bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have been found to have beneficial effects in cardiovascular disease, but only when administered via intramyocardial injection. The biodistribution of either intravenous or intramyocardial injection of MSC-EV in the presence of myocardial injury is uncharacterized at this time. Hypothesis: Intramyocardial injection will ensure delivery of MSC-EV to the ischemic myocardium, while intravenous injection will not. Methods: Human bone marrow mesenchymal stem cells were cultured, and MSC-EV were isolated and characterized. The MSC-EVs were then labeled with DiD lipid dye. FVB mice with normal cardiac function underwent left coronary artery ligation followed by either peri-infarct intramyocardial or tail vein injection of 3*10 6 or 2*10 9 particles of DiD-labeled MSC-EV or a DiD-saline control. The heart, lungs, liver, spleen and kidneys were harvested 2 hours post-injection and were submitted for fluorescent molecular tomography imaging. Results: Myocardial uptake of MSC-EV was only visualized after intramyocardial injection of 2*10 9 particles (p = 0.029), and was not detected after tail vein injection of MSC-EV (Figure 1). There were no significantly detectable MSC-EV uptake in other organs after intramyocardial injection, though there was possible focal lung uptake. After tail vein injection of MSC-EV, liver (p = 0.048) and spleen (p = 0.048) appeared to have diffuse MSC-EV uptake. Conclusions: Even in the presence of myocardial injury, only intramyocardial but not intravenous administration resulted in detectable levels of MSC-EV in the ischemic myocardium. This study confirms the role for intramyocardial injection in maximal and effective delivery of MSC-EV. Our ongoing studies aimed at developing bioengineered MSC-EV for targeted delivery to the heart may make MSC-EV clinically applicable.