EV4MI
- Research Leader:
- Antoni Bayes-Genis. MD, PhD
- Institution:
- Director, Heart Institute. Heart Institute, Germans Trias i Pujol University Hospital
- GCAT Input:
- Plasma samples
ST-segment elevation myocardial infarction (STEMI) management has evolved dramatically over the past decades, with significant reductions in STEMI-associated morbidity and mortality. However, despite use of early coronary reperfusion, the prevalence of STEMI-derived cardiogenic shock (STEMI-CS) has remained unaltered (5-8%), with high levels of mortality and resource utilization. To date, no therapeutic measure has consistently improved outcomes, despite the set with mechanical circulatory support.
Inflammation plays a key role in STEMI-CS and many inflammatory cytokines that are elevated in STEMI-CS are related to endothelial impairment, vascular permeability, and inappropriate vasodilation. This inflammatory cascade - the Systemic Inflammatory Response Syndrome (SIRS) - is typically associated with prolonged shock. We urgently need innovative measures to control SIRS. Mesenchymal stem cells (MSCs) showed promise as a therapy, via their paracrine effects.
Moreover, cumulative evidence has indicated that MSC-derived extracellular vesicles (EV) are crucial, active components of the immunosuppressive and reparative factors secreted by MSCs. Here, we aim to evaluate the inflammatory modulation potential of MSC-derived EVs in STEMI and STEMI-CS. First, we will perform a comprehensive proteomic characterization of the inflammatory response associated with STEMI (from Killip I to STEMI-CS). Second, we will evaluate the immune-modulating potential of EVs derived from the MSCs in Wharton-Jelly (MSC,WJ-EVs). Then, we will investigate EV biodistribution and toxicity in a murine model. Next, we will test EV safety and efficacy in a pre-clinical porcine MI model. Finally, we propose a first-inhuman clinical trial to test the safety of MSC,WJ-EVs in reperfused STEMI and STEMI-CS. This project opens a new approach to the treatment of the CS, an entity that has no effective treatment to date.
75 healthy subjects without cardiovascular disease from Prospective Study of Genomes of Catalonia (GCAT- Genomes for Life) have been selected (by age and sex) and analyzed as a control group for the first objective (perform a comprehensive analysis of the inflammatory molecular proteome associated with STEMI and STEMICS).
