Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes
Staton, C. C.; Widdess, M. A.; Jainarayanan, A.; Hoyle, A.; Williams, L.; Dominey-Foy, D.; Ulivieri, C.; Vendrell, I.; Fischer, R.; Baldari, C.; Nanchahal, J.; Gupta, D.; Cespedes-Donoso, P.; Wood, M. J. A.; Dustin, M. L.
Show abstract
Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytrens disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications.
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