Department of Respiratory Diseases, Hôpital Arnaud de Villeneuve, Montpellier F34000, France; CHU Montpellier, Institute for Regenerative Medicine and Biotherapy, Hôpital Saint-Eloi, Montpellier F34000, France; INSERM, U1183, Montpellier F34000, France; Université de MONTPELLIER, UFR de Médecine, Montpellier F34000, France.
CHU Montpellier, Institute for Regenerative Medicine and Biotherapy, Hôpital Saint-Eloi, Montpellier F34000, France.
Pharmacol Ther. 2018 Mar;183:58-77. doi: 10.1016/j.pharmthera.2017.10.002. Epub 2017 Oct 4.
Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the epithelium in response to injuries. Here, we review the key points of lung development, homeostasis and epithelial cell plasticity in response to injury and disease, because this knowledge is required to develop new lung disease treatments. Of note, canonical signaling pathways that are essential for proper lung development during embryogenesis are also involved in the pathophysiology of most chronic airway diseases. Moreover, the perfect control of these interconnected pathways is needed for the successful differentiation of induced pluripotent stem cells (iPSC) into lung cells. Indeed, differentiation of iPSC into airway epithelium and alveoli is based on the use of biomimetics of normal embryonic and fetal lung development. In vitro iPSC-based models of lung diseases can help us to better understand the impaired lung repair capacity and to identify new therapeutic targets and new approaches, such as lung cell therapy.
肺具有复杂的结构，由不同的细胞类型组成，这些细胞类型形成了大约 1700 万条输送气体的细支气管气道分支，这些气道分支与 5 亿个进行气体交换的肺泡相连。气道和肺泡由上皮细胞构成，在稳定状态下上皮细胞的更新率较低，但可以在受到损伤时再生上皮细胞。在这里，我们回顾了肺发育、内稳态以及上皮细胞在应对损伤和疾病时的可塑性的要点，因为这些知识是开发新的肺部疾病治疗方法所必需的。值得注意的是，在胚胎发生过程中对肺正常发育至关重要的经典信号通路也与大多数慢性气道疾病的病理生理学有关。此外，为了使诱导多能干细胞（iPSC）成功分化为肺细胞，需要对这些相互关联的通路进行完美的控制。事实上，iPSC 分化为气道上皮和肺泡是基于对正常胚胎和胎儿肺发育的生物模拟。基于 iPSC 的体外肺部疾病模型可以帮助我们更好地了解受损的肺修复能力，并确定新的治疗靶点和新的方法，如肺细胞治疗。
