INJURED LUNG AND ITS INFLUENCE ON MARROW CELL PHENOTYPE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目将研究受损肺细胞和骨髓细胞之间的细胞间通讯，以及这种通讯在肺损伤的骨髓细胞肺修复中的作用机制。我们实验室的研究已经证明，成年骨髓细胞是受损小鼠肺的归宿，并参与肺细胞的修复。我们假设，受损的肺细胞通过从肺细胞释放并随后被骨髓细胞摄取肺细胞来源的微泡来诱导骨髓细胞的表观遗传修饰，从而诱导骨髓细胞呈现肺细胞表型。其具体目的是：1.定义肺源性微泡的骨髓细胞群，包括整个骨髓细胞、各种骨髓分化细胞和纯化的造血干/祖细胞，并确定这些表型变化的持久性。2.确定肺源性微泡如何进入骨髓细胞，以及它们如何影响这些细胞的表型。3.明确细胞周期对骨髓细胞摄取肺源性微泡能力的影响。4.确定已摄取肺源性微泡或微泡的骨髓细胞移植是否参与了小鼠肺动脉高压模型的发病。最终，我们希望证明骨髓细胞具有足够的修复能力，为肺部疾病提供一种新的治疗选择，目前几乎没有有效的治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project will examine cell-to-cell communication between injured lung cells and bone marrow cells and mechanisms by which this communication aids in marrow cell-based lung repair of lung injury. Research from our laboratory has demonstrated that adult bone marrow cells home to injured murine lung and participate in the restoration of lung cells. We hypothesize that injured lung cells induce epigenetic modifications of marrow cells by release from lung cells and subsequent uptake by marrow cells of lung cell-derived microvesicles, thereby inducing marrow cells to assume a lung cell phenotype. The specific aims are to: 1. Define marrow cell populations which take up lung-derived microvesicles, focusing on whole bone marrow cells, various marrow-derived differentiated cells and purified hematopoietic stem/progenitor cells, and define the persistence of these phenotypic changes. 2. Determine how lung-derived microvesicles gain entry into marrow cells and how they influence the phenotype of these cells. 3. Define the influence of cell cycle on the ability of marrow cells to take up lung-derived microvesicles. 4. Determine if transplantation of marrow cells that have taken up lung-derived microvesicles or microvesicles themselves participate in the pathogenesis of murine models of pulmonary hypertension. Ultimately, we wish to demonstrate that marrow cells possess sufficient reparative properties to provide a novel therapeutic option for pulmonary diseases with few currently effective treatments.