Aging of Mesenchymal Stem Cells Missing Link in IPF

间充质干细胞的老化是 IPF 中缺失的环节

• 批准号: 8962475
• 负责人: Mauricio Rojas
• 金额: $ 50.27万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8962475
• 关键词: Address; Affect; Age; Aging; Animals; Automobile Driving; Biological; Biology; Bone Marrow; Bronchoalveolar Lavage; Cell Communication; Cell Separation; Cell Therapy; Cell physiology; Cells; Characteristics; Chronic; DNA Damage; Data; Defect; Development; Diagnosis; Disease; Effectiveness; Ensure; Environmental Risk Factor; Epithelial; Event; Exhibits; Exposure to; Fibrosis; Functional disorder; Gene Expression Profile; Genes; Hamman-Rich syndrome; Human; In Vitro; Incidence; Inflammatory; Infusion procedures; Injury; Interferons; Life Expectancy; Link; Lung; Lung diseases; Mediating; Mesenchymal; Mesenchymal Stem Cells; MicroRNAs; Modeling; Mus; Pathogenesis; Pathway interactions; Patients; Phenotype; Physiological; Predisposition; Prevalence; Process; Proliferating; Publishing; Recovery; Research; Resistance; Respiratory physiology; Rest; Risk; Risk Factors; Role; Severities; Signal Transduction; Stem cells; TNF gene; Telomere Shortening; Therapeutic; Therapeutic Intervention; Undifferentiated; Work; age effect; age related; aged; anergy; base; clinical application; exhaustion; functional disability; functional restoration; improved; in vivo; insight; interest; lung injury; lung repair; novel strategies; overexpression; premature; public health relevance; repaired; response; senescence; small hairpin RNA; stem cell biology; tissue repair

 DESCRIPTION (provided by applicant): The incidence of IPF and other pulmonary disorders increases with age independent of exposure to common environmental risk factors. Little is known about how age increases the risk for lung diseases. The lack of understanding the relationship between aging and the inability of the lung to repair after injury, as occurs in IPF, leads to an urgent need for more research in the field. Our own work has demonstrated an increase of susceptibility to chronic lung injury in aged mice. Additionally, we have described that bone marrow derived mesenchymal stem cells (B-MSCs) obtained from old mice are deficient in their multi-linage potential and in their capacity to respond to soluble factors. However, what are the biological consequences of an aged endogenous B-MSCs and why they exhibit a functional impairment is not well known. Our published and preliminary data supports the overarching and unique hypothesis that defective lung repair in aging is associated with dysfunctional activation, proliferation, and mobilization of B-MSCs. In the present revised project, we will focus on the effect of age on B-MSCs biology by comparing B-MSCs isolated from young and old donors and in the characteristics of B-MSCs during chronic Injury, by comparing B-MSCs isolated from IPF patients and age-matched and young controls. We are confident this will help us to understand the pathogenesis of other age-associated lung diseases and provide insights for the development of novel strategies for tissue repair.

 描述(由申请人提供)：IPF和其他肺部疾病的发病率随着年龄的增长而增加，与常见环境风险因素无关。关于年龄如何增加肺部疾病的风险，人们知之甚少。由于缺乏对衰老与肺损伤后无法修复的关系的了解，就像IPF所发生的那样，导致迫切需要在该领域进行更多研究。我们自己的工作表明，老年小鼠对慢性肺损伤的易感性增加。此外，我们还描述了从老年小鼠获得的骨髓间充质干细胞(B-MSCs)缺乏其多向分化潜能和对可溶性因子的反应能力。然而，衰老的内源性B-MSCs的生物学后果是什么，为什么它们表现出功能损害还不是很清楚。我们已发表的初步数据支持这一重要且独特的假设，即衰老过程中的肺修复缺陷与B-MSCs的激活、增殖和动员功能障碍有关。在本次修订的项目中，我们将通过比较年轻和老年供者的B-MSCs以及慢性损伤时B-MSCs的特性，通过比较IPF患者和年龄匹配的年轻对照组的B-MSCs，来关注年龄对B-MSCs生物学的影响。我们相信，这将有助于我们了解其他年龄相关肺部疾病的发病机制，并为开发新的组织修复策略提供见解。