Type II pneumocyte engraftment of bone marrow stem cells

骨髓干细胞的 II 型肺细胞植入

• 批准号: 6773802
• 负责人: Diane S Krause
• 金额: $ 36.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773802
• 关键词: SDS polyacrylamide gel electrophoresis; acute phase protein; apoptosis; bone marrow; bone marrow transplantation; cell differentiation; cell proliferation; fluorescence microscopy; fluorescent in situ hybridization; gene expression; genetically modified animals; green fluorescent proteins; hematopoietic stem cells; laboratory mouse; lung; lung lavage; northern blottings; respiratory epithelium; respiratory function; terminal nick end labeling; western blottings; whole body irradiation dosage

DESCRIPTION (provided by applicant): We and others have shown that epithelial cells lining the airways and the alveoli can be derived from bone marrow progenitor cells. These novel results have yet to be explored from an angle that addresses a functional role for these cells and the conditions that lead to their engraftment in the lung. To define the in vivo potential of bone marrow cells that differentiate into respiratory epithelium, we have designed experiments that combine quantification of engraftment with change in phenotype. We propose to investigate a role for bone marrow derived stem cells as progenitors of functional respiratory epithelium with the goal of using the results to develop novel and effective treatments for diseases of the lung. Specifically, we propose to test whether bone marrow transplantation can transfer a normally functioning gene to congenitally abnormal lungs, whether epithelial apoptosis is necessary for the engraftment of bone marrow cells as type I and type II cells, and whether these donor derived cells can reduce the lung damage associated with increased cell death. Using recipient mice whose pulmonary function is compromised due to knockout of the surfactant C protein, we will test the ability of bone marrow transplantation to confer normal phenotype to genetically abnormal lungs. To clarify the pathophysiology of the recipient lung tissue at the time of BMSC engraftment as epithelial cells, we will assess the necessity for epithelial apoptosis in the process of bone marrow engraftment as pneumocytes, and in order to gain a more fundamental understanding of the bone marrow derived stem cells that are capable of engraftment as epithelial cells, we will determine whether induction of stem cell proliferation is necessary for engraftment as lung epithelium.

描述（由申请人提供）：我们和其他人表明，气道和肺泡的上皮细胞可以源自骨髓祖细胞。这些新的结果尚未从一个角度探索，该角度解决了这些细胞的功能作用以及导致其在肺部植入的条件。为了定义骨髓细胞的体内潜力，分化为呼吸性上皮，我们设计了实验，将植入的定量与表型的变化结合在一起。我们建议研究骨髓衍生的干细胞作为功能性呼吸性上皮的祖细胞的作用，目的是利用结果来开发新的有效治疗肺部疾病。具体而言，我们建议测试骨髓移植是否可以将正常功能的基因转移到先天异常的肺部，是否需要上皮细胞凋亡对于I型和II型细胞的植入骨髓细胞以及这些供体衍生细胞是否可以减少与细胞死亡相关的肺损害。使用由于表面活性剂C蛋白敲除肺功能而受到损害的受体小鼠，我们将测试骨髓移植以赋予正常表型为基因异常肺的能力。 To clarify the pathophysiology of the recipient lung tissue at the time of BMSC engraftment as epithelial cells, we will assess the necessity for epithelial apoptosis in the process of bone marrow engraftment as pneumocytes, and in order to gain a more fundamental understanding of the bone marrow derived stem cells that are capable of engraftment as epithelial cells, we will determine whether induction of stem cell proliferation is necessary对于肺上皮的植入。