Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Curr Top Dev Biol. 2014;107:207-233. doi: 10.1016/B978-0-12-416022-4.00008-1.
The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of cell surface markers, these cells can also be isolated from murine and human lung and tested in 3D culture systems and in vivo transplant assays. The pathology of devastating lung diseases, including lung cancers, is likely in part due to dysregulation and dysfunction of lung stem cells. More precise characterization of stem cells with identification of new, unique markers; improvement in isolation and transplant techniques; and further development of functional assays will ultimately lead to new therapies for a host of human lung diseases. In particular, lung cancer biology may be greatly informed by findings in normal lung stem cell biology as evidence suggests that lung cancer is a disease that begins in, and may be driven by, neoplastic lung stem cells.
哺乳动物的肺是一个复杂的器官,包含许多假定的干细胞/祖细胞群体,这些群体有助于特定区域的组织稳态和修复。在这篇综述中,我们讨论了在肺稳态和疾病背景下鉴定和研究这些细胞群体的最新进展。遗传工程小鼠现在允许在不同类型的肺损伤修复过程中对几种肺干细胞和祖细胞群体进行体内谱系追踪。使用特定的细胞表面标志物集,这些细胞也可以从鼠类和人类肺中分离出来,并在 3D 培养系统和体内移植实验中进行测试。包括肺癌在内的破坏性肺病的病理学可能部分归因于肺干细胞的失调和功能障碍。通过鉴定新的、独特的标志物来更精确地表征干细胞;改进分离和移植技术;以及进一步开发功能测定,最终将为多种人类肺病带来新的治疗方法。特别是,正常肺干细胞生物学的发现可能会极大地推动肺癌生物学的发展,因为有证据表明肺癌是一种始于并可能由肿瘤性肺干细胞驱动的疾病。