| Popis: |
Background: In animal models, human bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have beneficial effects in cardiovascular disease (CVD) only when administered via intramyocardial injection. The biodistribution of either intravenous (IV) or intramyocardial injection of MSC-EV in the presence of myocardial injury is unknown. Methods: MSC-EV were isolated and labeled with DiD lipid dye. FVB mice underwent left coronary artery ligation followed by either peri-infarct intramyocardial or IV injection of 3*106 or 2*109 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*109 MSC-EV particles (p = 0.01), and was not detected after IV injection of MSC-EV (p > 0.9), compared to controls. There was no significantly detectable MSC-EV uptake in other organs after intramyocardial injection. After IV injection of 2*109 particles of MSC-EV, the liver (p = 0.02) and spleen (p = 0.04) appeared to have MSC-EV uptake. Conclusions: 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 render MSC-EV clinically applicable for CVD. |
