Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles

Abstract

Mesenchymal stromal/stem cells (MSCs) have been widely tested against many diseases, with more than 1000 registered clinical trials worldwide. Despite many setbacks, MSCs have been approved for the treatment of graft-versus-host disease and Crohn disease. However, it is increasingly clear that MSCs exert their therapeutic functions in a paracrine manner through the secretion of small extracellular vesicles (sEVs) of 50À200 nm in diameter. Unlike living cells that can persist long-term, sEVs are non-living and non-replicative and have a transient presence in the body. Their small size also renders sEV preparations highly amenable to sterilization by filtration. Together, acellular MSC-sEV preparations are potentially safer and easier to

Extracellular Vesicle-Based Therapy for COVID-19: Promises, Challenges and Future Prospects

“…Another limitation with EVs is the lack of standardized functional assays to determine the activity of EV preparations [163]. The techniques used in the isolation and purification of EVs for large-scale production have not been well standardized up to the gold standard, making it challenging to employ EVs as a therapeutic alternative [164].…”

From Mesenchymal Stromal Cells to Engineered Extracellular Vesicles: A New Therapeutic Paradigm

“…Although regulatory approval and safety of clinical application of EVs appears feasible, and may be simpler than cell-based therapy, important barriers that need to be addressed for clinical GMP-grade production of EVs include selection of the starting cellular material and optimizing cell culture, purification, quantification, and quality control ( Gowen et al, 2020 ). Understanding and determining the quantity, purity and potency of EVs, by the development of appropriate assays, will be an important part of the quality control criteria ( Gimona et al, 2021 ). Further challenges include issues of EV preservation and long-term stability, as we also go on to describe below.…”

Current understanding of the mesenchymal stem cell-derived exosomes in cancer and aging

“…More precise isolation and storage are important to be listed in guidelines to make this work more professional since many variables associated with the broad variety of MSC sources, culture systems and sEV enrichment processes should be taken in consideration. In addition to the course of action, MSC-therapeutic small EV's potential will also be impacted by micro-environment of an agonistic or antagonistic disease, path of delivery and timespan for therapeutic treatment in specific diseases [18] . It should be noted that different diseases should be handled in another way when it comes to therapeutic strategies involving exosomes.…”