Furthermore, the need for repetitive lot productions of cell source products can lead to greater batch-to-batch variability and the need for repeated manufacturing runs and testing time. Traditional EV production techniques are often limited due to the need for repeated and lengthy manufacturing protocols and characterization of each product lot. These challenges include establishing advanced characterization methods for documented reproducibility, the large-scale production of EV concentrated fluid, and the large-scale isolation and processing of clinical-grade, FDA-compliant EV products for Investigational New Drug enabling studies or clinical application. ĭespite promising pre-clinical data, several challenges impede the translation of EVs into cardiovascular clinics. Isolation of MSC-derived EVs from in vitro conditioned media has demonstrated important cardiac reparative effects, and thus further exploration is warranted. MSC-derived EVs promote tissue recovery through restoring tissue homeostasis, inhibiting inflammation, and promoting angiogenesis. EVs are important for cell-to-cell communication and produce a paracrine effect when used as a therapeutic agent. Pre-clinical data collected across multiple regenerative medicine models suggests that a primary mechanism of MSC-induced regeneration is mediated by the release of EVs into the extracellular space. Given the ability to purify EVs, it seems logical to test them for their ability to exert many of the actions of the parent cells. In terms of mechanism of action, there is growing awareness that MSCs release EVs and other growth factors that exert paracrine effects.

Phase I/II clinical trials such as POSEIDON, POSEIDON-DCM, and TRIDENT have demonstrated the safety and potential efficacy of allogeneic MSCs for the treatment of ischemic and non-ischemic cardiomyopathy. MSCs are found in many human organs and have been safely tested in clinical trials using an allogeneic strategy. Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) are presently under evaluation as a potential regenerative medicine approach. As the aged population continues to grow in number, novel therapies aimed at repairing the damaged cardiovascular system are required to provide effective medical solutions. One sentence summary: Large scale manufacturing of MSC-derived EVs is feasible and when delivered systemically, improves cardiac function after myocardial infarction.Ĭardiovascular aging is associated with molecular and physiological changes that result in the increased incidence of cardiovascular diseases such as hypertension, atherosclerosis, and myocardial infarction (MI). The systemic delivery of EV products improved cardiac function following myocardial infarctions as indicated by a significant improvement in ejection fraction as well as parameters of cardiac performance, afterload, contractility and lusitropy.Ĭonclusion: These findings have important implications for scale-up strategies of EVs and will facilitate clinical trials for their clinical evaluation. Our results demonstrate an advantage of the Quantum bioreactor as a large-scale platform for EV production using PLT media however, both media produced EVs with similar effects in vivo. We tested the potency of the EV products in a murine model of acute myocardial infarction. Methods and Results: We compared the efficiency of large scale MSC-derived EV production and characterized EV miRNA cargo using the Quantum bioreactor with either fetal bovine serum or human platelet lysate (PLT)-containing expansion media. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are under evaluation as a therapeutic option for the treatment of myocardial infarction.Īim: This study aimed to develop a large-scale manufacturing procedure to harvest clinical-grade EVs required for the translation of EVs to the clinic. Introduction: Cardiovascular disease and myocardial infarction are leading causes of morbidity and mortality in aged populations.

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