Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Respirology. 2013 Oct;18(7):1041-6. doi: 10.1111/resp.12112.
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF.
特发性肺纤维化 (IPF) 和慢性阻塞性肺疾病 (COPD) 是两种慢性、进行性和致命性的肺部疾病。IPF 和 COPD 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。目前,人们对衰老与慢性肺部疾病发展之间的关系知之甚少。有一种假设认为,慢性损伤会使肺部的局部和系统修复反应疲惫不堪。在衰老过程中,衰老细胞的逐渐积累会加剧这些变化。最近,干细胞已成为肺部损伤修复的关键机制。在这篇综述中,我们讨论了骨髓间充质干细胞 (B-MSC) 在肺损伤后的修复反应,以及它们的功能如何受到衰老的影响。我们自己的工作已经证明了 B-MSC 在几种急性和慢性肺损伤动物模型中的保护作用。我们最近使用动物模型证明了年龄与易发生严重损伤和纤维化的易感性之间存在关联。同时,我们已经确定了来自年轻和老年动物的 B-MSC 之间的功能差异。需要进一步的研究来了解衰老的 B-MSC 的功能障碍,最终导致快速的干细胞耗竭或疲劳,干扰它们在肺损伤中发挥保护作用的能力。阐明这些事件将有助于为 COPD 和 IPF 开发合理的新治疗策略。