Department of Clinical Sciences, Regenerative Medicine Laboratory, Tufts University Cummings School of Veterinary Medicine, North Grafton, Mass.
Division of Pulmonary, Critical Care, and Sleep Medicine, Brigham and Women's Hospital, Boston, Mass.
Transl Res. 2014 Apr;163(4):363-76. doi: 10.1016/j.trsl.2013.11.010. Epub 2013 Nov 21.
Lung regeneration research is yielding data with increasing translational value. The classical models of lung development, postnatal alveolarization, and postpneumonectomy alveolarization have contributed to a broader understanding of the cellular participants including stem-progenitor cells, cell-cell signaling pathways, and the roles of mechanical deformation and other physiologic factors that have the potential to be modulated in human and animal patients. Although recent information is available describing the lineage fate of lung fibroblasts, genetic fate mapping, and clonal studies are lacking in the study of lung regeneration and deserve further examination. In addition to increasing knowledge concerning classical alveolarization (postnatal, postpneumonectomy), there is increasing evidence for remodeling of the adult lung after partial pneumonectomy. Though limited in scope, compelling data have emerged describing restoration of lung tissue mass in the adult human and in large animal models. The basis for this long-term adaptation to pneumonectomy is poorly understood, but investigations into mechanisms of lung regeneration in older animals that have lost their capacity for rapid re-alveolarization are warranted, as there would be great translational value in modulating these mechanisms. In addition, quantitative morphometric analysis has progressed in conjunction with developments in advanced imaging, which allow for longitudinal and nonterminal evaluation of pulmonary regenerative responses in animals and humans. This review focuses on the cellular and molecular events that have been observed in animals and humans after pneumonectomy because this model is closest to classical regeneration in other mammalian systems and has revealed several new fronts of translational research that deserve consideration.
肺再生研究正在产生具有越来越高转化价值的数据。经典的肺发育模型、出生后肺泡化和肺切除后肺泡化，有助于更广泛地了解细胞参与者，包括干细胞-祖细胞、细胞间信号通路，以及机械变形和其他生理因素的作用，这些因素有可能在人类和动物患者中得到调节。尽管最近有信息描述了肺成纤维细胞的谱系命运、遗传命运图谱和克隆研究，但在肺再生研究中缺乏这些内容，值得进一步研究。除了增加对经典肺泡化（出生后、肺切除后）的了解外，还有越来越多的证据表明，成人肺在部分肺切除后会发生重塑。虽然范围有限，但大量引人注目的数据已经出现，描述了成人和大型动物模型中肺组织质量的恢复。对这种肺切除后长期适应的机制还了解甚少，但对失去快速再肺泡化能力的老年动物的肺再生机制的研究是有必要的，因为调节这些机制具有重要的转化价值。此外，定量形态计量学分析与先进成像技术的发展相结合，允许对动物和人类的肺再生反应进行纵向和非终末评估。本综述重点介绍了肺切除后在动物和人类中观察到的细胞和分子事件，因为该模型最接近其他哺乳动物系统中的经典再生，并且揭示了几个值得考虑的新的转化研究前沿。
