Abstract 12442: Extracellular Vesicles Engineered to Target Cardiomyocytes Demonstrate Improved Cardioprotection in a Mouse Model of Myocardial Infarction

• Published in: Circulation (New York, N.Y.) N.Y.), 2021-11, Vol.144 (Suppl_1), p.A12442-A12442
• Main Authors: Mentkowski, Kyle I, Manzanero, Cody A, Eagler, Lisa A, Lang, Jennifer K
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.144.suppl_1.12442

BackgroundCardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following myocardial infarction (MI). While extracellular vesicles (EVs) secreted by cardiosphere-derived cells (CDCs) have shown efficacy in promoting cardiac repair in large animal models of MI, their translational potential is limited by their biodistribution. To improve cardiac uptake, we previously engineered CDC-derived EVs to express a CM-specific binding peptide (CMP) on their surface. CMP-EVs demonstrated improved cardiac retention in vivo and decreased CM apoptosis in vitro when compared with non-targeted EVs. We hypothesized that targeting therapeutic EVs to CMs would result in further reduction of CM cell death in vivo and improvement in cardiac function post-MI. MethodsEVs were isolated from serum-free media as previously described and characterized by established protocols for size, morphology, and protein expression. To determine if CMP-EVs could enhance cardioprotection in vivo, we induced acute MI in adult C57BL/6 mice and randomized them to receive 1) EVs, 2) CMP-EVs or 3) vehicle control by IV and intramyocardial delivery according to approved institutional protocols. LVEF was assessed by echo at 1- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. ResultsCMP-EVs demonstrated superior cardiac targeting (IV route) and retention (intramyocardial route) when compared with control EVs 24 hours post MI (fold change of 1.8 ± 0.23 and 4.8 ± 2.3 respectively; n=8-10 mice/group, mean ± SEM, p