An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles

International Journal of Molecular Sciences, 2017 · DOI: 10.3390/ijms18071413 · Published: July 1, 2017

Simple Explanation

Mesenchymal stromal cells (MSCs) have regenerative and immunomodulatory properties, partly due to secreted factors in extracellular vesicles (EVs). These EVs are being explored as potential therapeutics. This study evaluates an in vitro assay to assess the immunomodulatory potential of MSC-derived EVs, focusing on their ability to inhibit T-cell proliferation. The assay measures the inhibitory effect of MSCs on induced T-cell proliferation and the mixed leukocyte reaction (MLR). MSC-derived EVs inhibited phytohemagglutinin-stimulated T-cell proliferation in a dose-dependent manner, similar to MSCs. However, only MSCs, not EVs, inhibited the alloantigen-driven MLR. These findings support the use of a cell-based in vitro assay for determining the immunomodulatory potential of EVs. Validating this assay could establish reliable criteria for EV release in future clinical studies, ensuring consistent therapeutic effects.

Study Duration

Not specified

Participants

Pooled peripheral blood mononuclear cells from ten randomly selected buffy coats from healthy donors

Evidence Level

In vitro study

Key Findings

1
MSC-derived EVs inhibit phytohemagglutinin (PHA)-stimulated T-cell proliferation in a dose-dependent manner, comparable to MSCs.
2
Inhibition of alloantigen-driven mixed leukocyte reaction (MLR) was observed for MSCs, but not for MSC-derived EVs.
3
EVs from both bone marrow (BM)- and umbilical cord (UC)-MSCs were equally potent in inhibiting T-cell proliferation.

Research Summary

This study evaluates a dual in vitro immunomodulation potency assay to monitor the immunomodulatory potential of MSC-derived EVs. The assay reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction. MSC-derived EVs inhibited phytohemagglutinin-stimulated T-cell proliferation in a dose-dependent manner, similar to MSCs. However, only MSCs, not EVs, inhibited the alloantigen-driven mixed leukocyte reaction. These results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies, addressing the current lack of suitable in vitro assays to monitor the therapeutic potential of EVs.

Practical Implications

Quality Control

The potency assay can be used as a quality control tool for MSC-EV production, ensuring consistent immunomodulatory potential.

Clinical Translation

Establishing reliable release criteria for EVs based on this assay can facilitate their application in clinical studies for various diseases.

EV Dosage

The finding that high doses of EVs are required for in vitro effects suggests that high doses may also be needed for in vivo applications, informing dosage strategies.

Study Limitations

1
The study is limited to in vitro conditions, and the results may not fully reflect in vivo responses.
2
The alloantigen-driven mixed leukocyte reaction inhibition was only observed for MSCs, not EVs, suggesting a limitation in the EVs' immunomodulatory capacity in this specific context.
3
The study acknowledges the lack of standardization in EV isolation, quantification, and characterization methods, which can affect the reproducibility and comparability of results.

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