Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

JOURNAL OF EXTRACELLULAR VESICLES, 2019 · DOI: 10.1080/20013078.2019.1609206 · Published: April 14, 2019

Simple Explanation

Mesenchymal stromal cells (MSCs) show promise for treating diseases, but their effects are often due to factors they release, particularly small extracellular vesicles (sEVs). These sEVs have shown therapeutic potential in preclinical studies. However, there are inconsistencies in MSC-sEV research due to differences in MSC sources, sEV production methods, and a lack of standardized testing. To address these issues, several scientific societies are proposing criteria to better define MSC-sEVs. These criteria aim to ensure that MSC-sEVs are well-characterized, with quantifiable metrics to identify their cellular origin, the presence of lipid-membrane vesicles, and the integrity of these vesicles, facilitating comparisons and advancing their clinical application.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
MSC-sEVs should be defined by quantifiable metrics to identify the cellular origin of the sEVs in a preparation.
2
MSC-sEV preparations should be classified according to their manufacturing process.
3
MSCs marker, CD73, CD90 and CD105, and the absence of CD14, CD34 and CD11b, could be used to identify MSCs cellular origin.

Research Summary

The inconsistencies in MSC-sEV research are due to the variability in MSC-sEV preparations from the starting cell source to the final product, coupled with a lack of standardized quality assurance assays and functional assays. Defining MSC-sEV products by the manufacturing process is not recommended for advancing the science and later-stage clinical applications of MSC-sEVs. A more practical approach would be to develop a set of minimal quantifiable metrics to harmonize the definition of MSC-sEVs and provide a denominator for comparative manufacturing and functional testing of different preparations.

Practical Implications

Data Sharing and Comparison

Harmonizing the definition of MSC-sEVs will allow for the comparison of different MSC-sEV preparations, and the differences in biology or therapeutic applications can be mapped to quantifiable differences in the defining features.

Quantifiable Metrics

The metrics identified include the ratio of MSC to non-MSC surface antigens, the ratio of membrane lipids to protein, the ratio of specific lipids, the concentration of membrane lipid vesicles, vesicle integrity, and biological activity.

Reference Standards

The next step is to quantify and validate each metric, using a well-characterized MSC-sEV preparation as a reference for each metric and assessing each metric by several independent laboratories to ensure robustness and reproducibility.

Study Limitations

1
Variability in MSC-sEV preparations.
2
Lack of standardized quality assurance assays and in vitro and in vivo functional assays.
3
The identified characteristics convey only the physical and biological integrity of EVs and may not predict therapeutic potency.

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