On May 1st, thought leaders from the ISEV and ISCT published online in Cytotherapy a joint statement, “ISEV and ISCT statement on EVs from MSCs and other cells: considerations for potential therapeutic agents to suppress COVID-19” (PMID: 32425691, DOI: 10.1016/j.jcyt.2020.05.002). On this note, we at RoosterBio would like to thank the authors for this thorough review of recent literature regarding use of extracellular vesicles (EVs) and exosomes for COVID-19 related illnesses, and for their sound recommendations.
While there appears to be a growing signal of clinical benefit across the preclinical literature to justify EV study, we emphatically agree that well-designed and scientifically rigorous clinical trials will be needed to establish more precise mechanisms of action. Identifying primary determinants of product quality, such as identity, potency, safety, and purity are central both to diligent product development and also a foundation for scalable manufacturing systems for these products. For example, the question of how MSC-EVs might promote tolerance, suppress inflammation, and signal into a paracrine milieu for chemotaxis of macrophages and other cells is not fully defined. In addition, possible attendant risks of variable clinical product quality need to be carefully assessed, such as thrombogenesis and suppression of anti-infection immunity, as well as the impact of manufacturing platforms and critical process parameters on these quality parameters.
We would like to especially highlight this important statement by the authors:
“To this end, it is imperative that stringent “identity” and “potency” parameters are defined and potential side effects addressed before MSC-EV or other EV preparations are released for therapeutic applications (Lener et al., 2015; Reiner et al., 2017; Witwer et al., 2019). To date, many groups use in-house MSC-EV manufacturing and characterization strategies, mainly for preclinical studies (Börger et al., 2017). Protocols fulfilling good manufacturing practice (GMP) criteria are sparse, and just a few have been published (Gimona et al., 2017; Pachler et al., 2017; Rohde et al., 2019). For product candidates, studies focusing on safety and clinical pharmacology need to be performed. Results of such studies are mandatory to provide guidance for adjustment of manufacturing, storage, dosing, and administration of EV- based therapeutics in specific target diseases.”
To promote progress in this promising and compelling new area of clinical research, we are fully aligned with these words and in committing them to action. Accordingly, we at RoosterBio are continually looking to advance manufacturing and enable product developers to accelerate the translation of next generation regenerative cures.
As sponsors of both ISCT and ISEV, we are proud to be in support of these societies’ core values and mission, and to the imperative, “do no harm.” To all clinical product developers in the MSC-EV space, RoosterBio is here to help you not just to avoid harm, but to carefully and methodically “do good,” both to the suffering COVID-19 patients and to this nascent industry we share.