Role of Lung MSC in Emphysema

描述（由申请人提供）：拟议的研究将使用创新的方法来扩展我们对肺干细胞的知识，以拓宽与nhlbi相关的肺部疾病的治疗范例。因此，我们假设通过Wnt/¿-catenin信号传导维持肺间充质干细胞功能对于肺组织稳态是必要的。我们建议在体外和体内使用新的小鼠模型来检查肺msc依赖的异常肺结构和功能的机制。我们将确定成人肺间充质干细胞在体内对肺组织结构和功能的影响机制。此外，我们将通过体外和体内新系统确定Wnt/¿-catenin信号调节肺间充质干细胞功能和影响组织稳态的机制。这些模型将使我们能够确定一种适合作为治疗靶点的细胞类型。此外，这些研究将产生重要的资源和试剂，这将是科学界和医学界的巨大兴趣。

DESCRIPTION (provided by applicant): The proposed studies will use innovative approaches to expand upon our knowledge of lung stem cells to broaden treatment paradigms for NHLBI-related lung diseases. We therefore hypothesize that the maintenance of lung MSC function by Wnt/¿-catenin signaling is necessary for pulmonary tissue homeostasis. We propose to examine lung MSC-dependent mechanisms of abnormal pulmonary architecture and function using novel mouse models both in vitro and in vivo. We will determine the mechanism by which adult lung MSCs contribute to pulmonary tissue architecture and function in vivo. In addition, we will determine the mechanism by which Wnt/¿-catenin signaling regulates lung MSCs function and affects tissue homeostasis using both in vitro and in vivo novel systems. These models will enable us to identify a cell type which may be suited as a therapeutic target. Additionally, these studies will generate important resources and reagents that will be of vast interest to both the scientific and medical communities.