Extracellular Vesicles from Wharton's Jelly Mesenchymal Stem Cells Suppress CD4 Expressing T Cells Through Transforming Growth Factor Beta and Adenosine Signaling in a Canine Model
Authors
Crain, Sarah K.Robinson, Sally R.
Thane, Kristen E.
Davis, Airiel M.
Meola, Dawn M.
Barton, Bruce A.
Yang, Vicky K.
Hoffman, Andrew M.
UMass Chan Affiliations
Department of Quantitative Health SciencesDocument Type
Journal ArticlePublication Date
2019-02-01Keywords
MSCWharton's jelly
exosomes
extracellular vesicles
immune modulation
Cell Biology
Developmental Biology
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
Mesenchymal stem cells (MSCs) are widely investigated as potential therapeutic agents due to their potent immunomodulatory capacity. Although specific mechanisms by which MSC acts on immune cells are emerging, many questions remain, including the potential of extracellular vesicles (EVs) to mediate biological activities. Canine MSCs are of interest for both veterinary and comparative models of disease and have been shown to suppress CD4(pos) T cell proliferation. The aim of this study was to determine whether EV isolated from canine Wharton's jelly-derived MSC (WJ-MSC EV) suppresses CD4(pos) T cell proliferation using biochemical mechanisms previously ascribed to soluble mediators [transforming growth factor beta (TGF-beta) and adenosine]. WJ-MSC EV exhibited mode of 125 nm diameter, low buoyant density (1.1 g/mL), and expression of EV proteins Alix and TSG101. Functionally, EVs inhibited CD4(pos) T cell proliferation in a dose-dependent manner, which was absent in EV-depleted samples and EVs from non-MSC fibroblasts. EV suppression of CD4(pos) T cell proliferation was inhibited by a TGF-betaRI antagonist, neutralizing antibodies to TGF-beta, or A2A adenosine receptor blockade. TGF-beta was present on EVs as latent complexes most likely tethered to EV membrane by betaglycan. These data demonstrate that canine WJ-MSC EV utilizes TGF-beta and adenosine signaling to suppress proliferation of CD4(pos) T cell and will enable further investigation into mechanisms of immune cell modulation, as well as refinement of WJ-MSC and their EVs for therapeutic application.Source
Stem Cells Dev. 2019 Feb 1;28(3):212-226. doi: 10.1089/scd.2018.0097. Epub 2019 Jan 14. Link to article on publisher's site
DOI
10.1089/scd.2018.0097Permanent Link to this Item
http://hdl.handle.net/20.500.14038/46786PubMed ID
30412034Related Resources
ae974a485f413a2113503eed53cd6c53
10.1089/scd.2018.0097