Lung regeneration and translational implications of the postpneumonectomy model.
Lung regeneration and translational implications of the postpneumonectomy model.
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DOI：
10.1016/j.trsl.2013.11.010
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
K. Thane;E. Ingenito;A. Hoffman
中科院分区：
文献类型：
--
作者：
K. Thane;E. Ingenito;A. Hoffman
肺再生研究正在产生具有越来越大的转化价值的数据。肺发育、出生后肺泡化和肺切除术后肺泡化的经典模型有助于更广泛地理解细胞参与者，包括干祖细胞、细胞-细胞信号传导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被调节。虽然最近的信息描述了肺成纤维细胞的谱系命运，但在肺再生的研究中缺乏遗传命运作图和克隆研究，值得进一步研究。除了增加有关经典肺泡化（出生后，肺切除术后）的知识外，越来越多的证据表明部分肺切除术后成人肺重塑。虽然范围有限，但已经出现了令人信服的数据，描述了成年人和大型动物模型中肺组织质量的恢复。肺切除术长期适应的基础还不清楚，但对失去快速肺泡化能力的老年动物肺再生机制的研究是必要的，因为调节这些机制将具有很大的转化价值。此外，定量形态学分析与先进成像技术的发展相结合，可以对动物和人类的肺再生反应进行纵向和非终末评价。这篇评论的重点是在动物和人类肺切除术后观察到的细胞和分子事件，因为这个模型是最接近经典的再生在其他哺乳动物系统，并揭示了一些新的前沿转化研究，值得考虑。
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.