Mesenchymal Stromal Cell-Derived PTX3 Promotes Wound Healing via Fibrin Remodeling

Cappuzzello, C. et al. J. Invest. Dermatol. 2016, 136: 293-300.

Speaker: Yi-Hsin Hsiao (蕭宜馨)                                 Time: 13:10~14:00, March 17, 2016

Commentator: Dr. Bei-Chang Yang (楊倍昌 教授)    Place: Room 601

Abstract:

Cutaneous wound healing is a complex process that requires collaborative efforts of different mediators as well as tissues and cell lineages. Deregulation of normal wound healing processes may result in fibrosis, scarring, and loss of tissue function. Mesenchymal stromal cells (MSCs) are multipotent stromal cells that exist in many tissues and are capable of differentiating into several different cell types. Exogenously administered MSCs migrate to damaged tissue sites, where they participate in tissue repair. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. Previous study has shown that PTX3 can bind fibrinogen/fibrin and plasminogen at acidic pH and increase plasmin-mediated fibrinolysis. In this study, the authors studied the effect of Ptx3-deficient (Ptx3^-/-) MSCs on the cutaneous wound healing. They found that PTX3 deficiency in MSCs resulted in delayed wound closure. Furthermore, there was a significant reduction in the Ptx3^-/- MSCs recruited to the wound site. Increased fibrin deposition and reduced D-dimer, the pericellular fibrinolysis product, in the wounds were also noted in the Ptx3^-/- MSC-treated skins. Moreover, the migration index through the fibrin was significantly lower in Ptx3^-/- MSCs. Taken together, these results not only indicate that PTX3 acts as a potent promoter of tissue repair and remodeling exerted by MSCs, but also provide evidence of a therapeutic approach for nonhealing wounds.

References:

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2.         Doni, A. et al. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. J. Exp. Med. 2015; 212:905-25.