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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Injury minimization after myocardial infarction: focus on extracellular vesicles
Lucio Barile1,2, Eduardo Marbán3
1Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, CH-6500, Bellinzona, Switzerland.
Insights
Extracellular vesicles (EVs) show promise as a cardioprotective therapy after heart attacks, offering advantages over traditional cell treatments. Large animal studies and early clinical trials suggest EVs are a viable, potentially off-the-shelf option for improving heart function.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Biotechnology
Background:
- Acute myocardial infarction (AMI) still has high mortality, particularly in patients with low left ventricular ejection fraction (LVEF).
- Existing cell therapies for cardiac repair show limited success, necessitating novel cardioprotective strategies.
- Extracellular vesicles (EVs) are emerging as a promising cell-mimetic therapy for cardiovascular diseases.
Purpose of the Study:
- To review the translational potential of extracellular vesicle (EV)-based therapies for cardioprotection after myocardial infarction.
- To highlight findings from large-animal studies evaluating EV efficacy and safety.
- To summarize ongoing early-stage clinical trials of EV therapies in cardiology.
Main Methods:
- Review of preclinical data, focusing on large-animal models of myocardial infarction.
- Analysis of the biological properties of EVs, including their cargo and paracrine mechanisms.
- Synopsis of current clinical trial landscape for EV-based cardiac therapies.
Main Results:
- EVs, derived from mesenchymal and cardiac stromal progenitor cells, demonstrate safety and efficacy in preclinical settings.
- EVs offer clinical advantages over cell therapy, including stability, storage potential, and reduced immunogenicity.
- Large-animal studies support the therapeutic potential of EVs for cardiac repair post-infarction.
Conclusions:
- EV-based therapies represent a promising advancement in regenerative medicine for treating myocardial infarction.
- The unique properties of EVs facilitate their development into 'off-the-shelf' therapeutic products.
- Ongoing clinical trials are crucial for validating the efficacy and safety of EV therapies in human patients.
Abstract:
Despite improvements in clinical outcomes following acute myocardial infarction, mortality remains high, especially in patients with severely reduced left ventricular ejection fraction (LVEF <30%), emphasizing the need for effective cardioprotective strategies adjunctive to recanalization. Traditional cell therapy has shown equivocal success, shifting the focus to innovative cardioactive biologicals and cell mimetic therapies, particularly extracellular vesicles (EVs). EVs, as carriers of non-coding RNAs and other essential biomolecules, influence neighbouring and remote cell function in a paracrine manner. Compared to cell therapy, EVs possess several clinically advantageous traits, including stability, ease of storage (enabling off-the-shelf clinical readiness), and decreased immunogenicity. Allogeneic EVs from mesenchymal and/or cardiac stromal progenitor cells demonstrate safety and potential efficacy in preclinical settings. This review delves into the translational potential of EV-based therapeutic approaches, specifically highlighting findings from large-animal studies, and offers a synopsis of ongoing early-stage clinical trials in this domain.
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