Homing and Differentiation of Adult Stem Cells to Lung

描述（由申请人提供）： 这项申请旨在促进两个相邻机构的四组研究人员之间的合作研究，这些研究人员将开发有关成体干细胞治疗重要肺部疾病的潜在有用性的明确数据。工作人员包括一组具有成体干细胞制备和表征专业知识的研究人员，两组具有纤维化和肺气肿等疾病动物模型专业知识的研究人员，以及第四组具有开发用于纠正遗传性疾病囊性纤维化（CF）的病毒载体的专业知识。这项研究将集中在一类特殊的成体干细胞上，这种干细胞可以从患者自己的骨髓中分离出来，被称为间充质干细胞或骨髓基质细胞（MSC）。该计划的项目格式将允许研究人员通过执行无法与个人研究赠款进行的协作工作来推进该领域。将在创新的共培养系统中测试三个表征良好的MSC亚群，该系统定量测定其修复受损肺细胞的潜力。我们还将探讨细胞融合可能在MSC修复肺细胞中发挥作用的可能性。此外，它将使用一种新的竞争性移植试验来确定哪种MSC亚群在免疫缺陷小鼠的肺中最有效地移植。将在石棉肺损伤模型和气管外植体模型中测定三个细胞亚群的植入和分化。 将测试三个细胞亚群在肺气肿弹性蛋白酶模型中修复肺损伤的有效性。此外，我们将尝试确定骨髓间充质干细胞在肺内移植的机制。 来自CF患者的MSC将被工程化以纠正基因缺陷，然后进行测试以确定它们是否可以成为功能性纤毛上皮细胞。随着实验的进行，研究人员必须迅速分享数据。例如，数据将表明MSC的哪些亚群应在其他三个项目中进行测试。作为另一个例子，使用慢病毒开发的经验将使使用病毒追踪MSC成为可能。

DESCRIPTION (provided by applicant): This application is to foster collaborative research among four groups of investigators at two neighboring institutions that will develop definitive data about the potential usefulness of adult stem cells to treat important pulmonary diseases. The staff includes one group of investigators with expertise in the preparation and characterization of adult stem cells, two groups of investigators with expertise in animal models for diseases such as fibrosis and emphysema, and a fourth group with expertise in the development of viral vectors for correction of the genetic disease cystic fibrosis (CF). The research will focus on the special class of adult stem cells that can be isolated from a patient's own bone marrow and that are referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The program project format will allow the investigators to advance the field by performing collaborative work that cannot be carried out with individual research grants. Three sub-populations of MSCs that are well characterized will be tested in an innovative co-culture system that assays quantitatively their potential for repairing damaged pulmonary cells. We will also explore the possibility that cell fusion may play a role in the repair of pulmonary cells by MSCs. In addition, it will use a new assay for competitive engraftment to determine which sub-population of MSCs engrafts most efficiently in lungs of immunodeficient mice. The three sub-populations of cells will be assayed for engraftment and differentiation in a model for lung damage by asbestos and in a tracheal explant model. The three sub-populations of cells will be tested for their effectiveness in repairing lung damage in an elastase model for emphysema. In addition, we will attempt to define the mechanisms by which MSCs engraft in lung. MSCs from patients with CF will be engineered to correct the gene defect and then tested to determine whether they can become functional ciliated epithelial cells. Of necessity, the investigators will have to quickly share data as their experiment progresses. For example, data will suggest which sub-populations of MSC should be tested in the other three projects. As another example, the experience developed with lentiviruses will make it possible to use viruses for tracking MSCs.