International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

Cytotherapy, 2020 · DOI: https://doi.org/10.1016/j.jcyt.2020.05.002 · Published: May 2, 2020

Simple Explanation

The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) acknowledge the potential of extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) as a treatment for COVID-19. However, they do not currently endorse the use of EVs or exosomes for any purpose in COVID-19 pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight. This statement emphasizes the need for rigorous scientific, regulatory, and ethical guidelines for clinical uses of EVs, including well-characterized preparations produced under strict GMP conditions and proper regulatory oversight.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
MSC-EVs do not necessarily suppress immune responses, but rather modulate them, specifically moderating acute immune responses toward regulatory responses, inducing tolerance, and restoring homeostasis.
2
The source of MSC-EVs matters, as MSCs from different tissues and even from different donors can display functional differences, affecting the cytokine content and therapeutic potency of the EVs.
3
Adipose-derived MSC-EVs had higher thrombogenic activity than bone marrow-derived MSC-EVs, indicating that the source of parental cells might increase thrombosis risk.

Research Summary

This statement addresses the potential use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as a therapeutic approach for COVID-19, highlighting both the promise and the potential risks. While pre-clinical data suggest MSC-EVs can modulate immune responses and attenuate lung injury, the specific scientific rationale for their use in COVID-19 needs to be better understood. The document stresses the importance of stringent "identity" and "potency" parameters and addressing potential side effects before MSC-EVs are used therapeutically, advocating for well-characterized EV preparations produced under strict GMP conditions.

Practical Implications

Standardization of EV Production

Establish robust, scalable manufacturing processes for EV production, including immortalized clonal MSC lines rigorously tested for EV production and potency.

Clinical Trial Design

Design rational clinical trials with appropriate regulatory oversight, focusing on safety and clinical pharmacology, to guide the adjustment of manufacturing, storage, dosing, and administration of EV-based therapeutics.

Ethical Considerations

Ensure that clinical uses of EVs follow appropriate scientific, regulatory, and ethical guidelines, including obtaining informed consent from patients and complying with good clinical practice, even in compassionate use settings.

Study Limitations

1
The specific scientific rationale for MSC-EV administration in COVID-19 patients needs to be better understood.
2
MSCs are a heterogeneous cell entity, and functional differences can be observed based on tissue origin.
3
Protocols fulfilling Good Manufacturing Practice (GMP) criteria are sparse.

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