title: Mesenchymal Stromal Cell-Derived PTX3 Promotes Wound Healing via Fibrin Remodeling.
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.
authors.affiliation: Centro Ricerca Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappuzzello
authors.affiliation: IRCCS-Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.affiliation: Centro Ricerca Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Dander
authors.affiliation: IRCCS-Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.affiliation: Pathology Unit, L. Sacco Department of Clinical Sciences, L. Sacco Hospital, Università degli Studi di Milano, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.affiliation: IRCCS-Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: IRCCS-Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Centro Ricerca Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: IRCCS-Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Centro Ricerca Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy. Electronic address: giovanna.damico@hsgerardo.org.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Amico
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011859:Radiography; D011897:Random Allocation; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000000981:diagnostic imaging* / Q000628:therapy; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D005337:Fibrin; D009419:Nerve Tissue Proteins; D000099153:Pentraxins