Department of Anatomy and 2Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Am J Respir Crit Care Med. 2012 Dec 15;186(12):1213-9. doi: 10.1164/rccm.201207-1151PP. Epub 2012 Sep 20.
The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.
探索患病成人肺部的内源性再生潜能代表了一项创新和令人兴奋的任务。在这个肺部视角下，我们讨论了内源性肺修复和再生所必需的三个主要组成部分：上皮祖细胞群体、调节其修复和再生潜能的发育信号通路，以及人类患病肺部的周围细胞外基质。在过去的几年中，已经在肺部中发现了几个不同的上皮祖细胞群体，所有这些群体都可能在不同程度上对不同的损伤做出反应。显然，几个祖细胞群体相互参与维持和修复，这受到 Wnt 或 Notch 信号等发育信号通路的高度调控。第三，内源性祖细胞和发育信号通路与细胞外基质密切协同作用。这三个组成部分定义和细化了肺部的高度动态微环境，在几种慢性肺部疾病中，这种微环境以特定疾病的方式发生改变。寻找合适的混合物以诱导患病肺部的有效和可控修复和再生的研究正在进行中，并将为慢性肺部疾病患者的治疗开辟全新的途径。
