Alveolar wars: The rise of in vitro models to understand human lung alveolar maintenance, regeneration, and disease.,STEM CELLS Translational Medicine

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Alveolar wars: The rise of in vitro models to understand human lung alveolar maintenance, regeneration, and disease.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-04-09 , DOI: 10.1002/sctm.19-0433
Kelly V Evans _{1,

2} , Joo-Hyeon Lee _{1,

2}

Affiliation

Diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and bronchopulmonary dysplasia injure the gas‐exchanging alveoli of the human lung. Animal studies have indicated that dysregulation of alveolar cells, including alveolar type II stem/progenitor cells, is implicated in disease pathogenesis. Due to mouse‐human differences, there has been a desperate need to develop human‐relevant lung models that can more closely recapitulate the human lung during homeostasis, injury repair, and disease. Here we discuss how current single‐cell RNA sequencing studies have increased knowledge of the cellular and molecular composition of human lung alveoli, including the identification of molecular heterogeneity, cellular diversity, and previously unknown cell types, some of which arise specifically during disease. For functional analysis of alveolar cells, in vitro human alveolar organoids established from human pluripotent stem cells, embryonic progenitors, and adult tissue from both healthy and diseased lungs have modeled aspects of the cellular and molecular features of alveolar epithelium. Drawbacks of such systems are highlighted, along with possible solutions. Organoid‐on‐a‐chip and ex vivo systems including precision‐cut lung slices can complement organoid studies by providing further cellular and structural complexity of lung tissues, and have been shown to be invaluable models of human lung disease, while the production of acellular and synthetic scaffolds hold promise in lung transplant efforts. Further improvements to such systems will increase understanding of the underlying biology of human alveolar stem/progenitor cells, and could lead to future therapeutic or pharmacological intervention in patients suffering from end‐stage lung diseases.

中文翻译：

肺泡战争：了解人类肺泡维持、再生和疾病的体外模型的兴起。

特发性肺纤维化、慢性阻塞性肺病和支气管肺发育不良等疾病会损害人肺的气体交换肺泡。动物研究表明，肺泡细胞（包括肺泡 II 型干细胞/祖细胞）的失调与疾病发病机制有关。由于小鼠与人类之间的差异，迫切需要开发与人类相关的肺部模型，以更准确地再现人类肺部在稳态、损伤修复和疾病过程中的情况。在这里，我们讨论当前的单细胞 RNA 测序研究如何增加对人类肺泡细胞和分子组成的了解，包括识别分子异质性、细胞多样性和以前未知的细胞类型，其中一些细胞类型是在疾病期间特别出现的。为了对肺泡细胞进行功能分析，从健康和患病肺部的人多能干细胞、胚胎祖细胞和成人组织建立的体外人肺泡类器官模拟了肺泡上皮的细胞和分子特征。强调了此类系统的缺点以及可能的解决方案。芯片上的类器官和离体系统，包括精密切割的肺切片，可以通过提供肺组织的进一步细胞和结构复杂性来补充类器官研究，并且已被证明是人类肺部疾病的宝贵模型，同时无细胞的生产合成支架在肺移植工作中大有希望。对此类系统的进一步改进将增加对人类肺泡干/祖细胞的基础生物学的了解，并可能导致未来对患有终末期肺病的患者进行治疗或药物干预。

更新日期：2020-04-09

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