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Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review
An Duong1, Gaganvir Parmar2, Aidan M Kirkham3
1Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Background Aims:
Interest in cell-based therapy using extracellular vesicles (EVs) is intensifying, building upon promising preclinical research and a handful of published clinical studies. Registered clinical trials remain small, heterogeneous in design and underpowered to determine safety and efficacy on their own. A scoping review of registered studies can identify opportunities to pool data and perform meta-analysis.
Methods:
Registered trials were identified by searching clinical trial databases (Clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry) on June 10, 2022.
Results:
Seventy-three trials were identified and included for analysis. Mesenchymal stromal cells (MSCs) were the most common cell type from which EVs were derived (49 studies, 67%). Among the 49 identified MSC-EV studies, 25 were controlled trials (51%) with a combined total of 3094 participants anticipated to receive MSC-derived EVs (2225 in controlled studies). Although EVs are being administered to treat a broad range of conditions, trials treating patients with coronavirus disease-2019 and/or acute respiratory distress syndrome were observed most commonly. Despite heterogeneity between studies, we anticipate that at least some of the studies could be combined in meaningful meta-analysis and that a combined sample size of 1000 patients would provide the ability to detect a ≥5% difference in mortality with MSC-EVs compared to controls and could be achieved by December 2023.
Conclusions:
This scoping review identifies potential barriers that may stall clinical translation of EV-based treatment, and our analysis calls for more standardized product characterization, use of quantifiable product quality attributes and consistent outcome reporting in future clinical trials.
Insights
Extracellular vesicle (EV) clinical trials are growing but lack standardization. This review of 73 trials highlights the need for consistent reporting to enable data pooling and advance cell-based therapies.
Area of Science:
- Cellular and Molecular Medicine
- Regenerative Medicine
- Biotechnology
Background:
- Interest in extracellular vesicles (EVs) for cell-based therapy is increasing, fueled by preclinical data.
- Current clinical trials for EVs are limited in size and design, hindering definitive safety and efficacy assessments.
- A scoping review is crucial for identifying opportunities to aggregate data from registered EV studies.
Approach:
- A comprehensive search of major clinical trial registries (ClinicalTrials.gov, WHO ICTRP, Chinese Clinical Trial Registry) was conducted on June 10, 2022.
- Seventy-three registered trials involving EVs were identified and analyzed.
- Mesenchymal stromal cell-derived EVs (MSC-EVs) were the most prevalent, with 49 studies identified.
Key Points:
- Mesenchymal stromal cell-derived EVs (MSC-EVs) dominate current research, with 49 studies identified.
- The majority of MSC-EV trials (51%) are controlled, involving over 3000 participants.
- Trials for COVID-19 and ARDS are most common, indicating therapeutic focus.
- Despite heterogeneity, potential for meta-analysis exists, with a target of 1000 patients to detect significant mortality differences with MSC-EVs.
Conclusions:
- This review identifies barriers to the clinical translation of EV-based therapies.
- Standardized product characterization is essential for future EV clinical trials.
- Adoption of quantifiable product quality attributes and consistent outcome reporting is recommended.
