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

基本信息

批准号：
9298707
负责人：
Mauricio Rojas
金额：
$ 47.53万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/9298707
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 Cellular biology Characteristics Chronic DNA Damage Data Defect Development Diagnosis Disease Effectiveness Ensure Environmental Risk Factor Epithelial Event Exhibits Exposure to Fibrosis Functional disorder Genes Hamman-Rich syndrome Human In Vitro Incidence Inflammatory Infusion procedures Injury Interferons Life Expectancy Link Lung Lung diseases Mediating Mesenchymal Differentiation Mesenchymal Stem Cells MicroRNAs Modeling Mus Myelofibrosis Pathogenesis Pathway interactions Patients Phenotype Physiological Predisposition Prevalence Process Proliferating Publishing Pulmonary Fibrosis 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 bone aging clinical application exhaustion functional disability functional restoration improved in vivo insight interest lung injury lung repair mouse model novel strategies overexpression premature public health relevance repaired response senescence small hairpin RNA tissue repair transcriptome

项目摘要

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，与常见环境危险因素的暴露无关。人们对年龄如何增加肺部疾病的风险知之甚少。缺乏对衰老与肺部疾病之间关系的了解。肺部损伤后无法修复，如特发性肺纤维化（IPF），导致迫切需要在该领域进行更多研究，我们自己的工作已证明老年小鼠对慢性肺损伤的易感性增加。骨髓来源来自老年小鼠的间充质干细胞 (B-MSC) 缺乏多谱系潜力和对可溶性因子的反应能力，然而，衰老的内源性 B-MSC 会产生什么生物学后果以及它们为何表现出功能障碍。我们发表的初步数据支持这一总体且独特的假设，即衰老过程中的肺修复缺陷与 B-MSC 的功能失调性激活、增殖和动员有关。年龄通过比较从年轻和年老供体中分离的 B-MSC 以及从 IPF 患者和年龄匹配的年轻对照中分离的 B-MSC 的慢性损伤期间的特征，我们有信心这将是关于 B-MSC 生物学的研究。帮助我们了解其他与年龄相关的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。