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.

Cappuzzello, C., Doni, A., Dander, E., Pasqualini, F., Nebuloni, M., Bottazzi, B., et al. (2016). Mesenchymal stromal cell-derived PTX3 promotes wound healing via fibrin remodeling. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136(1), 293-300 [10.1038/JID.2015.346].

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

CAPPUZZELLO, CLAUDIA
Primo
;
DANDER, ERICA;BIONDI, ANDREA;
2016

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.
Articolo in rivista - Articolo scientifico
PTX3; Wound Healing; Fibrin Remodeling
English
293
300
8
Cappuzzello, C., Doni, A., Dander, E., Pasqualini, F., Nebuloni, M., Bottazzi, B., et al. (2016). Mesenchymal stromal cell-derived PTX3 promotes wound healing via fibrin remodeling. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136(1), 293-300 [10.1038/JID.2015.346].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/97377
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