Characterization and treatment of the scarred vocal fold

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.