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Int. J. Mol. Sci. 2017, 18(7), 1413; doi:10.3390/ijms18071413

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

1
GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria
2
Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria
3
Institute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria
4
University Clinic for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University (PMU), Lindhofstrasse 20, 5020 Salzburg, Austria
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 28 April 2017 / Revised: 9 June 2017 / Accepted: 29 June 2017 / Published: 1 July 2017
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Abstract

The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs) is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs) exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our 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. View Full-Text
Keywords: extracellular vesicles; exosomes; T-cell proliferation; immune modulation; mesenchymal stromal cells; mesenchymal stem/progenitor cells extracellular vesicles; exosomes; T-cell proliferation; immune modulation; mesenchymal stromal cells; mesenchymal stem/progenitor cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pachler, K.; Ketterl, N.; Desgeorges, A.; Dunai, Z.A.; Laner-Plamberger, S.; Streif, D.; Strunk, D.; Rohde, E.; Gimona, M. An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles. Int. J. Mol. Sci. 2017, 18, 1413.

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