Annexin A1'containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Giovanna Leoni, Philipp Alexander Neumann, Nazila Kamaly, Miguel Quiros, Hikaru Nishio, Hefin R. Jones, Ronen Sumagin, Roland S. Hilgarth, Ashfaqul Alam, Gabrielle Fredman, Ioannis Argyris, Emile Rijcken, Dennis Kusters, Chris Reutelingsperger, Mauro Perretti, Charles A. Parkos, Omid C. Farokhzad, Andrew S. Neish, Asma Nusrat*

*Corresponding author for this work

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.

Original languageEnglish (US)
Pages (from-to)1215-1227
Number of pages13
JournalJournal of Clinical Investigation
Volume125
Issue number3
DOIs
StatePublished - Mar 2 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Leoni, G., Neumann, P. A., Kamaly, N., Quiros, M., Nishio, H., Jones, H. R., Sumagin, R., Hilgarth, R. S., Alam, A., Fredman, G., Argyris, I., Rijcken, E., Kusters, D., Reutelingsperger, C., Perretti, M., Parkos, C. A., Farokhzad, O. C., Neish, A. S., & Nusrat, A. (2015). Annexin A1'containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. Journal of Clinical Investigation, 125(3), 1215-1227. https://doi.org/10.1172/JCI76693