P4: BM-DERIVED STEM CELLS HOMING AND LUNG CELL PRODUCTION IN INJURED LUNG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目的具体目标是：1)评估影响骨髓细胞产生肺细胞的变量；2)评估骨髓和肺细胞对损伤的反应以及影响骨髓细胞向受损肺归巢的因素；以及3)将目标1和2中概述的最佳归巢和肺细胞产生条件应用于两种不同的小鼠损伤模型的骨髓移植：博莱霉素诱导的肺纤维化和弹性酶诱导的肺气肿。我们和其他人已经证明，在肺损伤的背景下，骨髓细胞能够参与各种肺细胞的产生。此外，还有人在特定的损伤模型中证明了骨髓细胞输注后损伤肺的组织学和功能改善(博莱霉素损伤的小鼠肺胶原含量降低，野百合碱损伤的大鼠肺高压降低)。我们希望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，目前对这些疾病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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims of this project are: 1) To evaluate the variables that influence lung cell production from marrow cells; 2) To evaluate marrow and lung cells response to injury and factors influencing the homing of marrow cells to injured lung; and 3) Apply optimal homing and lung cell production conditions, as outlined in aims 1 and 2, to marrow transplantation in two separate mouse-injury models: bleomycin-induced pulmonary fibrosis and elastase-induced emphysema. We and others have demonstrated that marrow cells are capable of participating in the production of various lung cells in the setting of lung injury. Furthermore, others have demonstrated histological and functional improvement of the injured lung after marrow cell infusion in specific injury models (decreased lung collagen content in bleomycin-injured mice, decreased pulmonary hypertension in monocrotaline-injured rats). Our hope is that marrow cells possess sufficient reparative properties to provide a novel therapeutic option for pulmonary diseases for which there are few effective treatments.