Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction

Davidson, Sarah J; Roncalli, Jérôme; Sürder, Daniel; Corti, Roberto; Chugh, Atul R.; Yang, Phillip C.; Henry, Timothy D.; Stanberry, Larissa; Lemarchand, Patricia; Beregi, Jeau-Paul; Traverse, Jay H.

doi:10.1016/j.ahj.2023.02.004

American Heart Journal

2023

DOI: 10.1016/j.ahj.2023.02.004

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Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction

Sarah J Davidson

Jérôme Roncalli

Daniel Sürder

et al.

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2024

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Cited by 2 publications

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Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

Roncalli,

Roubille,

Meyer

et al. 2024

ESC Heart Failure

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AimsThe extent of irreversible cardiomyocyte necrosis after acute myocardial infarction (AMI) is a major determinant of residual left ventricular (LV) function and clinical outcome. Cell therapy based on CD34+ cells has emerged as an option to help repair the myocardium and to improve outcomes. The dose of CD34+ cells and the route of administration are two important factors that will determine the clinical effectiveness of the approach, provided it is robust and feasible. Here, we describe the rationale and design of the multicentre open‐label randomized controlled phase I/IIb trial evaluating the safety and the likelihood of efficacy of transendocardial expanded CD34+ cell administration in patients presenting with AMI and a reduced LV ejection fraction.MethodsPatients with a large AMI and LV ejection fraction <50% are randomized 3:1 to transendocardial expanded CD34+ cell injection plus standard of care or standard of care alone. Patients randomized to intervention are treated with lenograstim for 5 days before 220 ± 10 mL blood cell harvest from which autologous CD34+ cells are purified and expanded for 9 days using an automated good manufacturing practice compliant platform. The primary endpoint is the incidence of major adverse cardiac events over 6 months. The main secondary endpoints are LV end systolic volume index and the viability of the infarcted segments.ConclusionsAutologous CD34+ cell therapy is currently limited by technological constraints. This is the first trial to evaluate the feasibility and potential effect of CD34+ cells after automated expansion and transendocardial administration in patients with large AMI.

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Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

Roncalli,

Roubille,

Meyer

et al. 2024

ESC Heart Failure

View full text Add to dashboard Cite

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Injury minimization after myocardial infarction: focus on extracellular vesicles

Barile,

Marbán

2024

European Heart Journal

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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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Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction

Cited by 2 publications

References 22 publications

Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

Injury minimization after myocardial infarction: focus on extracellular vesicles

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