Characterization of immune response in vocal fold injury and tissue regeneration

声带损伤和组织再生中免疫反应的表征

• 批准号: 8603765
• 负责人: Suzanne N. King
• 金额: $ 3.72万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603765
• 关键词: Address; Affect; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Architecture; Behavior; Biocompatible Materials; Blood; Cell Communication; Cell Proliferation; Cell Therapy; Cells; Characteristics; Cicatrix; Clinical; Complex; Disease; Exhibits; Extracellular Matrix; Family suidae; Future; Goals; Healed; Heterogeneity; Human; Hydrogels; Immune; Immune response; Immune system; Immunologics; Implant; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Influentials; Injury; Intervention; Knowledge; Lamina Propria; Larynx; Lead; Macrophage Activation; Measures; Mesenchymal Stem Cells; Methods; Modeling; Molecular; Natural regeneration; Necrosis; Operative Surgical Procedures; Outcome; Pathogenesis; Phase; Phenotype; Play; Prevention; Process; Property; Regulation; Research; Resolution; Role; Stromal Cells; Surgical Injuries; Techniques; Therapeutic; Tissue Engineering; Tissues; Voice; Work; Wound Healing; angiogenesis; base; healing; in vivo; insight; macrophage; monocyte; new therapeutic target; next generation; novel; prevent; public health relevance; response; response to injury; therapy development; tissue regeneration; tissue repair; treatment strategy; vocal cord

DESCRIPTION (provided by applicant): Vocal fold scarring is one of the most challenging, recalcitrant, and functionally debilitating conditions affecting the human voice. Treatment progress for vocal fold scarring is hindered by our limited understanding of the immunological architecture of the larynx, specifically the role of macrophages and their response to inflammation. Injuries to the vocal fold (i.e. surgical) trigger a highly complex wound healing response, involving resident and infiltrating macrophages that resolve inflammation and initiate tissue repair by expressing a cascade of inflammatory mediators that breakdown extracellular matrix components, eliminate necrotic cells and debris, and promote angiogenesis and stromal cell proliferation. Considering the complex cellular and molecular components involved in wound healing, it is necessary to confront and understand the immunological activity that controls inflammation and the healing cascade, which is central to many fibrotic disorders. The goal of this project is to identify macrophage behavior regulating scar formation and assess the interaction of these cells with cell based therapeutic approaches for tissue regeneration. In this application we will 1) Characterize macrophage function in the vocal fold lamina propria using pig surgical injury model 2) Measure the effects of MSC-hydrogel constructs on macrophage function and resolution of inflammation using a pig surgical injury model. We will demonstrate that macrophages play a dual role in the resolution of inflammation through regulation of both pro- and anti- inflammatory responses throughout the wound healing process, which can affect the pathogeneses of vocal fold scar. We hypothesis that macrophages residing in the lamina propria will express distinct classical and alternative activated phenotypes, depending on the phase of wound healing (i.e. inflammation, proliferation, remodeling). Findings from this proposal will characterize macrophage function in the vocal fold lamina propria, providing vital insight into the pathogeneses and treatment of vocal fold scar. An understanding of macrophage behavior may allow us to manipulate future tissue engineering strategies for vocal fold scar, with direct, anti-inflammatory benefits.

描述（由申请人提供）：声带疤痕是影响人类声音的最具挑战性，最具顽固性和功能使人衰弱的条件之一。我们对喉部的免疫结构的有限理解，特别是巨噬细胞的作用及其对炎症的反应，使人声折叠疤痕的治疗进展受到了阻碍。发声折叠的伤害（即手术）触发了高度复杂的伤口愈合反应，涉及居民和浸润巨噬细胞，通过表达一系列炎症介体来解决炎症并启动组织修复，从而破坏细胞外基质成分，消除细胞外基质细胞，消除坏死细胞和脱发细胞，并促进血管生成，并促进血管生成，并促进血管生成。考虑到与伤口愈合有关的复杂细胞和分子成分，有必要面对和了解控制炎症和愈合级联反应的免疫学活动，这对于许多纤维化疾病至关重要。 该项目的目的是确定调节疤痕形成的巨噬细胞行为，并评估这些细胞与基于细胞的治疗方法的相互作用。在此应用中，我们将使用Pig手术损伤模型2）测量MSC-Hydregel构建体对巨噬细胞功能的影响以及使用Pig手术损伤模型来解决炎症的影响。我们将证明巨噬细胞在整个伤口愈合过程中调节促炎和抗炎反应在炎症的分辨率中起着双重作用，这可能会影响声带疤痕的病原体。我们假设驻留于椎板中的巨噬细胞将根据伤口愈合的相（即炎症，增殖，重塑），表达不同的经典和替代激活的表型。 该提案的发现将表征声带薄片的巨噬细胞功能，从而为病原体和人声折叠疤痕的治疗提供了重要的见解。对巨噬细胞行为的理解可能会使我们能够操纵未来的组织工程策略，从而具有直接的，抗炎的益处。