Mast Cell Activity During Scar Maturation: Multiple Sequential Time Point Analysis In-vivo Show Its Unique Localisation And Role In Skin Healing
Sara Ud-Din1, Mohamed Baguneid2, Douglas McGeorge3, Martin Barron1, Silvia Bulfone-Paus1, Ardeshir Bayat1
1University of Manchester, Manchester, United Kingdom, 2Manchester University NHS Foundation Trust, Manchester, United Kingdom, 3Nuffield Health Chester Hospital, Chester, United Kingdom
BACKGROUND Mast cells (MCs) provide mediators during wound healing and enhance acute inflammation, stimulate re-epithelialisation, angiogenesis as well as promote scarring. Their exact role in cutaneous repair remains ill-understood. Moreover, there is a paucity of evidence of their role and activity over time in human skin in vivo in cutaneous wound healing and scarring.
METHODS We utilised objective noninvasive devices (full-field laser perfusion imaging (FLPI) and dynamic-optical coherence tomography (D-OCT) and detailed gene and protein studies to evaluate the time course of MC recruitment in a human wound healing model. 5mm skin-biopsies were performed on day 0 to the upper inner arms of 62 healthy volunteers, then the wounds/scars were excised at different time intervals (weeks (W)1,2,3,4,5,6,8).
RESULTS MC tryptase (MCT) and chymase (MCC) analysis demonstrated that normal unwounded skin was populated with few MCs (MCT:15cells/mm2,MCC:12cells/mm2) as opposed to wounded skin and scar tissue. After reaching a maximum density at W1 compared to baseline (MCT:44cells/mm2,p=0.002; MCC:41cells/mm2,p=0.04), the MC density decreased by W8 (MCT:26cells/mm2,p=0.003; MCC:20cells/mm2,p=0.01) reaching a level similar to that observed in normal unwounded skin. Inflammation analysis by IL6 corroborated this trend with intensity values highest at W1 compared to baseline (p=0.04). VEGFA and CD31analysis confirmed the angiogenic activity of these proteases. Expression significantly increased from baseline (VEGFA:18.7%;CD31:41vessels/mm2) to W3 (VEGFA:72.8%,p=0.01; CD31:335vessels/mm2,p=0.002) and reduced to W8 (VEGFA:45.3%,p=0.02;CD31:157vessels/mm2,p=0.009). Clinical data for blood flow measured by FLPI and D-OCT supported these results demonstrating a significant increase from unwounded skin (FLPI:107.9Pu, D-OCT:0.078Au) to W1 (FLPI:394.9Pu,p<0.001; D-OCT:0.145Au,p<0.001) and reduction to W8 (FLPI:130Pu,p=0.0003; D-OCT:0.107Au,p=0.002 ).
CONCLUSIONS For the first time in healing wounds and early scar maturation in human skin, we demonstrate the localisation of MC and its potential role in healing. These findings may help towards better understanding of the role of MC in cutaneous wound healing and scar maturation.
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