Abstract 16213: No Cardiac Benefit After Single Dose of Intramyocardial or Intravenous Mesenchymal Stem Cell-Derived Extracellular Vesicles Post-Myocardial Infarction Supports Need for Bioengineered Extracellular Vesicles With Non-Invasive Cardiac Uptake

Abstract

Introduction: In pre-clinical models, mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have benefits in ischemic CVD. We previously showed that only intramyocardial (IM) injection of MSC-EV, an invasive method of administration, and not intravenous (IV) injection, resulted in reliable cardiac uptake after acute MI. No prior studies have compared the functional outcome of IM versus IV injection after acute MI. Hypothesis: IM injection of MSC-EV will result in improved cardiac outcomes whereas IV injection will not. Aim: To demonstrate the long-term outcomes of IM versus IV MSC-EV after acute MI. Methods: MSC-EV were isolated and characterized. FVB mice underwent left anterior descending coronary artery ligation and subsequent injection of the following: 1) IM saline control (IM-C; n = 8), 2) IM 2*10 9 MSC-EV particles (IM-EV; n = 9), 3) IV saline control (IV-C; n = 8), and 4) IV 2*10 9 MSC-EV particles (IV-EV; n = 8). The mice underwent pre-operative, and post-operative weekly echocardiograms. On post-operative day 28, the mice were euthanized, and the hearts were harvested. Results: Preliminary data showed no significant differences in left ventricular ejection fraction (p = 0.6151) or fractional shortening (p = 0.1135) in the IM-EV and IV-EV groups compared to the controls IM-C and IV-C, respectively, at post-operative day 28 (Figure 1A). There were also no significant differences in infarct size (p = 0.05620) (Figure 1B) or anterior border zone fibrosis (p = 0.6333) (Figure 1C) on Masson-Trichrome staining. Conclusions: Preliminary findings demonstrate that a one-time IM or IV dose of MSC-EV given immediately after acute MI results in no observable effects. Additional MSC-EV doses after MI may produce beneficial effects. Results from our ongoing studies on the creation of stem cells bioengineered to produce MSC-EV with surface cardiac targeting peptides and immune-evasion properties will be presented in August 2023.