Journal
STEM CELLS
Volume 36, Issue 1, Pages 79-90Publisher
WILEY
DOI: 10.1002/stem.2730
Keywords
Mesenchymal stromal cells; Mesenchymal stem cells; Extracellular vesicles; Exosomes; Microvesicles; Inflammation; Current good manufacturing practices
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Funding
- Center for Clinical and Translational Sciences Training Award, University of Texas McGovern Medical School [5KL2-TR000370-10]
- Ladybug
- Glassell Family Stem Cell Research Fund
- Ansh Labs
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Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been proposed to be a key mechanistic link in the therapeutic efficacy of cells in response to cellular injuries through paracrine effects. We hypothesize that inflammatory stimulation of MSCs results in the release of EVs that have greater anti-inflammatory effects. The present study evaluates the immunomodulatory abilities of EVs derived from inflammation-stimulated and naive MSCs (MSCEv(+) and MSCEv, respectively) isolated using a current Good Manufacturing Practice-compliant tangential flow filtration system. Detailed characterization of both EVs revealed differences in protein composition, cytokine profiles, and RNA content, despite similarities in size and expression of common surface markers. MSCEv(+) further attenuated release of pro-inflammatory cytokines in vitro when compared to MSCEv, with a distinctly different pattern of EV-uptake by activated primary leukocyte subpopulations. The efficacy of EVs was partially attributed to COX2/PGE(2) expression. The present study demonstrates that inflammatory stimulation of MSCs renders release of EVs that have enhanced anti-inflammatory properties partially due to COX2/PGE(2) pathway alteration.
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