Logo

American Heart Association

  2
  0


Final ID: MDP1327

Surface Engineering Enhances the Therapeutic Potential of Systemically Delivered Extracellular Vesicles Following Acute Myocardial Infarction

Abstract Body (Do not enter title and authors here): Background: Cardiomyocyte (CM) cell death is a sentinel event in the development of cardiomyopathy. It contributes to additional myocyte dysregulation, generating a positive-feedback loop which potentiates the evolution of heart disease. Accordingly, CMs represent an important therapeutic target in modulating the pathogenesis of cardiac disease. While extracellular vesicles derived from cardiosphere-derived cells (CDC-EVs) have emerged as therapeutic vectors for cardiovascular disease, their potential is limited by their biodistribution and necessity for direct intramyocardial injection. We hypothesized that CDC-derived EVs engineered to express a CM-specific binding peptide (CMP-EVs) with improved cardiac targeting would result in enhanced therapeutic efficacy when administered intravenously post-myocardial infarction (MI).

Methods: Mice with acute MI underwent both intramyocardial and intravenous (IV) delivery of unmodified CDC-EVs, CMP-EVs and vehicle control in a double-blind study. Left ventricular ejection fraction (LVEF) was assessed by echo at 2- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints.

Results: Mice treated with IV delivered CMP-EVs demonstrated a significant improvement in LVEF (57% ± 2% vs. 47% ± 3%) and a significant reduction in remote zone cardiomyocyte apoptosis (0.6 ± 0.2% vs. 1.9 ± 0.4%) when compared with IV delivered non-targeted EVs at 28-days post-MI (n=6-8 mice per group, mean± SEM, p<0.05, one-way ANOVA followed by Tukey’s post-hoc test).

Conclusions: Systemic administration of CMP-EVs enhances their ability to augment systolic function following acute MI when delivered via systemic route, demonstrating a strategy to optimize therapeutic EV delivery post-MI. This approach also facilitates repeated dosing which may be advantageous as a treatment strategy for several cardiovascular diseases.
  • Tarvirdizadeh, Touba  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Mentkowski, Kyle  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Manzanero, Cody  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Eagler, Lisa  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Potekar, Gayatri  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Lang, Jennifer  ( Jacob's School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , New York , United States )
  • Author Disclosures:
    Touba Tarvirdizadeh: DO NOT have relevant financial relationships | Kyle Mentkowski: DO NOT have relevant financial relationships | Cody Manzanero: DO NOT have relevant financial relationships | Lisa Eagler: DO NOT have relevant financial relationships | Gayatri Potekar: No Answer | Jennifer Lang: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Interorgan/Intercellular Communication in Myocardial Injury

Monday, 11/18/2024 , 11:10AM - 12:40PM

Moderated Digital Poster Session

More abstracts on this topic:
Gelatin hydrogel elasticity influences TBX18-induced pacemaker cell behavior

Choi Younghwan, Fan Jinqi, Cho Hee Cheol

A Novel Multivariate Scoring System for Diagnosing Post-Myocardial Infarction Pericarditis Following Percutaneous Coronary Intervention

Bolaji Olayiwola, Omoru Okiemute, Upreti Prakash, Echari Blanche, Shoar Saeed, Basit Jawad, Alraies M Chadi

More abstracts from these authors:
The Impact of Shear-Thinning Hydrogel Delivery on Extracellular Vesicle Cardiac Retention

Tarvirdizadeh Touba, Alaa Mohamed Mohamed, Andreadis Stelios, Lang Jennifer

You have to be authorized to contact abstract author. Please, Login
Not Available