Nature：揭示肺部组织再生的新机制

  刊登在国际杂志Nature上的一篇研究论文中，来自美国杰克逊实验室(Jackson Laboratory)的科学家们揭示了特定的肺部干细胞在因疾病损伤的肺部再生过程中的重要作用。
  研究者McKeon表示，肺部可以再生的理论在生物医学研究领域一时半会儿还不能被接受，部分原因是由于严重肺部疾病比如慢性阻塞性肺疾病（COPD）及肺纤维化患者疾病治疗效果的持续下滑。尽管如此研究者指出，在人类中仍然存在肺部再生的强大系统，比如有些急性呼吸窘迫综合症（ARDS）幸存者在肺部组织被明显破坏后仍可以恢复正常的肺部功能。
  小鼠似乎也具有这样的能力，感染H1N1流感病毒的小鼠肺部表现出了明显的进行性炎症，而且其重要的肺部细胞种类不断减少，但感染后数周，小鼠的肺部依然可以恢复至正常状态。利用这种小鼠模型，研究人员鉴别出了名为p63+/Krt5+的肺部干细胞，当对p63+/Krt5+进行培养时，其可以形成肺泡样结构，类似于肺部组织中的肺泡；当小鼠模型感染H1N1后这些肺部干细胞就会迁移至肺部炎性位点，装配形成泡状结构从而恢复小鼠肺部的功能。
  为了检测p63+/Krt5+是否可以用于肺部组织再生，研究人员开发了一种新型系统，其可以利用基因工具选择性地移除小鼠肺部的干细胞；结果显示，缺失p63+/Krt5+的小鼠在感染H1N1后不能恢复肺部的正常功能，当单一的肺部干细胞被分离出来并且移植入损伤的肺部后，其会不断形成肺部腺泡，恢复肺部功能。研究者希望本文的研究或为开发治疗急性呼吸窘迫综合征等肺部疾病的新型疗法提供希望。（转化医学网360zhyx.com）
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p63+Krt5+ distal airway stem cells are essential for lung regeneration
Nature doi:10.1038/nature13903
Wei Zuo, Ting Zhang, Daniel Zheng'An Wu, Shou Ping Guan, Audrey-Ann Liew, Yusuke Yamamoto, Xia Wang, Siew Joo Lim, Matthew Vincent, Mark Lessard, Christopher P. Crum, Wa Xian & Frank McKeon
Lung diseases such as chronic obstructive pulmonary disease1 and pulmonary fibrosis2 involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia3, 4 or acute respiratory distress syndrome5, 6 often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASCp63/Krt5, to this process7. Here we show that pre-existing, intrinsically committed DASCp63/Krt5 undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASCp63/Krt5 in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASCp63/Krt5-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.