Aging of Mesenchymal Stem Cells Missing Link in IPF

 描述（由申请人提供）：特发性肺纤维化和其他肺部疾病的发生率随着年龄的增长而增加，与暴露于常见环境风险因素无关。人们对年龄如何增加肺部疾病的风险知之甚少。由于对衰老与肺损伤后无法修复（如IPF）之间的关系缺乏了解，因此迫切需要在该领域进行更多研究。 我们自己的工作已经证明了老年小鼠对慢性肺损伤的易感性增加。此外，我们已经描述了从老年小鼠获得的骨髓间充质干细胞（B-MSCs）缺乏其多谱系潜能和对可溶性因子的反应能力。然而，老化的内源性B-MSCs的生物学后果是什么以及为什么它们表现出功能障碍还不清楚。我们发表的和初步的数据支持总体和独特的假设，即老化中有缺陷的肺修复与B-MSC的功能失调激活，增殖和动员有关。在目前修订的项目中，我们将通过比较从年轻和老年供体分离的B-MSCs，以及通过比较从IPF患者分离的B-MSCs和年龄匹配的年轻对照，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性肺部疾病的发病机制，并为开发组织修复的新策略提供见解。

 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.