Yaron Jordan R, Zhang Liqiang, Guo Qiuyun, Awo Enkidia A, Burgin Michelle, Schutz Lauren N, Zhang Nathan, Kilbourne Jacquelyn, Daggett-Vondras Juliane, Lowe Kenneth M, Lucas Alexandra R
Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Department of Animal Care and Technologies, Arizona State University, Tempe, AZ 85287, USA.
Pharmaceutics. 2020 Oct 22;12(11):1003. doi: 10.3390/pharmaceutics12111003.
Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or "fine tune" the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.
复杂的皮肤伤口带来了重大的医疗和经济负担，尤其是在糖尿病、感染和高龄等合并症的情况下。加速、改善或“微调”愈合过程以提高皮肤伤口愈合和管理质量的新方法，是深入研究的重点。在此，我们研究了一种重组免疫调节蛋白的局部应用，该蛋白可抑制趋化因子与糖胺聚糖的相互作用，在小鼠夹板全层切除伤口模型中减少有害或过度的炎症反应。M-T7是一种37 kDa分泌型病毒衍生糖蛋白，已在众多炎症免疫病理学动物模型中显示出治疗效果。与单独用生理盐水治疗相比，重组M-T7局部治疗显著加速了伤口愈合。愈合的伤口表现出改善的组织重塑特性，这由胶原蛋白成熟度决定。M-T7治疗加速了愈合伤口周围的血管生成速率，同时TNF、VEGF和CD31水平升高。M-T7治疗后的免疫细胞反应与CCL2水平的维持以及表达精氨酸酶-1的M2巨噬细胞和CD4 T细胞丰度增加有关。因此，重组M-T7局部治疗可促进愈合伤口中的促消退环境，具有作为皮肤组织修复新治疗方法的潜力。
