Characterization and treatment of the scarred vocal fold

项目摘要/摘要 声带黏膜损伤导致的瘢痕形成是一个令人衰弱和具有挑战性的临床问题。 对此没有统一有效的治疗方法。新兴研究，包括在我们的 最近的资金周期表明，非居民、迁移细胞可能发挥重要的和以前的 在室颤伤口愈合和组织重塑中的作用被低估。具有特殊重要性的迁移细胞 VF粘膜的维持和修复是单核细胞谱系中的那些，出现了一个多样化的群体 来自骨髓内的髓系祖细胞。基于这样一个科学前提，即骨髓来源， 单核细胞系细胞是伤口愈合结果的关键影响因素，我们提出了一套明确的实验方案 这将量化骨髓来源的细胞向正常和受损的VF粘膜的迁移(目标1)，识别 单核细胞系细胞在VF后炎症信号和纤维化转归中的功能作用 粘膜损伤(目标2)，并确定单核细胞系细胞中和后的发声结果 人源化VF大鼠粘膜损伤模型(目标3)。这项拟议的研究将定义 单核细胞系细胞可获得性和VF伤口愈合结果，并进一步为未来提供基础 从事VF疤痕预防方面的工作。

Project Summary/Abstract Vocal fold (VF) mucosal injury resulting in scar formation is a debilitating and challenging clinical problem for which there is no uniformly effective treatment. Emerging research, including work completed during our most recent funding cycle, suggests that non-resident, migratory cells may play an important and previously underappreciated role in VF wound healing and tissue remodeling. The migratory cells of particular importance to VF mucosal maintenance and repair are those within the monocyte lineage, a diverse population that arises from myeloid progenitor cells within bone marrow. Based on the scientific premise that bone marrow-derived, monocyte-lineage cells are key effectors of wound healing outcome, we propose a definitive set of experiments that will quantify bone marrow-derived cell migration to normal and injured VF mucosa (Aim 1), identify the functional contribution of monocyte-lineage cells to inflammatory signaling and fibrosis outcome following VF mucosal injury (Aim 2), and determine phonatory outcomes following monocyte-lineage cell neutralization in a humanized rat model of VF mucosal injury (Aim 3). The proposed research will define the relationship between monocyte-lineage cell availability and VF wound healing outcome and, further, provide a foundation for future work in the area of VF scar prophylaxis.