Mesenchymal stromal cell-derived PTX3 promotes wound healing via fibrin remodeling

Claudia Cappuzzello, Andrea Doni, Erica Dander, Fabio Pasqualini, Manuela Nebuloni, Barbara Bottazzi, Alberto Mantovani, Andrea Biondi, Cecilia Garlanda, Giovanna D'Amico

Research output: Contribution to journalArticlepeer-review

Abstract

Although mesenchymal stromal cells (MSCs) can promote wound healing in different clinical settings, the underlying mechanism of MSC-mediated tissue repair has yet to be determined. Because a nonredundant role of pentraxin 3 (PTX3) in tissue repair and remodeling has been recently described, here we sought to determine whether MSC-derived PTX3 might play a role in wound healing. Using a murine model of skin repair, we found that Ptx3-deficient (Ptx3-/-) MSCs delayed wound closure and reduced granulation tissue formation compared with wt MSCs. At day 2, confocal microscopy revealed a dramatic reduction in green fluorescent protein (GFP)-expressing Ptx3-/-MSCs recruited to the wound, where they appeared to be not only poorly organized in bundles but also scattered in the extracellular matrix. These findings were further confirmed by quantitative biochemical analysis of GFP content in wound extracts. Furthermore, Ptx3-/-MSC-treated skins displayed increased levels of fibrin and lower levels of D-dimer, suggesting delayed fibrin-rich matrix remodeling compared with control skins. Consistently, both pericellular fibrinolysis and migration through fibrin were found to be severely affected in Ptx3-/-MSCs. Overall, our findings identify an essential role of MSC-derived PTX3 in wound repair underscoring the beneficial potential of MSC-based therapy in the management of intractable wounds.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalJournal of Investigative Dermatology
Volume136
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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