Institute of Human Genetics PAS, Strzeszynska 32, 60-479, Poznan, Poland.
Cell Commun Signal. 2021 May 27;19(1):63. doi: 10.1186/s12964-021-00740-z.
Human airway epithelial (HAE) cellular models are widely used in applicative studies of the airway physiology and disease. In vitro expanded and differentiated primary HAE cells collected from patients seem to be an accurate model of human airway, offering a quicker and cheaper alternative to the induced pluripotent stem cell (iPSCs) models. However, the biggest drawback of primary HAE models is their limited proliferative lifespan in culture. Much work has been devoted to understand the factors, which govern the HAE cell proliferation and differentiation, both in vivo and in vitro. Here, I have summarized recent achievements in primary HAE culture, with the special emphasis on the models of conditionally reprogrammed cells (CRC), which allow longer in vitro proliferation and differentiation of HAE cells. The review compares the CRC HAE technique variants (feeder culture or HAE mono-culture), based on recently published studies exploiting this model. The advantages and limitations of each CRC HAE model variant are summarized, along with the description of other factors affecting the CRC HAE culture success (tissue type, sampling method, sample quality).
CRC HAE cultures are a useful technique in respiratory research, which in many cases exceeds the iPSCs and organoid culture methods. Until the current limitations of the iPSCs and organoid culture methods will be alleviated, the primary CRC HAE cultures might be a useful model in respiratory research. Airway epithelium (AE) is a type of tissue, which lines the whole length of human airways, from the nose to the bronchi. Improper functioning of AE causes several human airway disorders, such as asthma, chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Much work has been devoted to finding the best scientific model of human AE, in order to learn about its functioning in health and disease. Among the popular AE models are the primary in vitro cultured AE cells collected from human donors. Unfortunately, such human AE (HAE) cells do not easily divide (expand) in vitro; this poses a large logistic and ethical problem for the researchers. Here, I summarize recent achievements in the methods for in vitro culture of human AE cells, with special emphasis on the conditionally reprogrammed cell (CRC) models, which allow longer and more effective expansion of primary human AE cells in vitro. The review describes how the specific chemicals used in the CRC models work to allow the increased HAE divisions and compares the effects of the different so-far developed variants of the CRC HAE culture. The review also pinpoints the areas which need to be refined, in order to maximize the usefulness of the CRC AE cultures from human donors in research on human airway disorders. Video abstract.
人类气道上皮 (HAE) 细胞模型广泛应用于气道生理学和疾病的应用研究。从患者中体外扩增和分化的原代 HAE 细胞似乎是人类气道的准确模型，为诱导多能干细胞 (iPSC) 模型提供了更快、更经济的替代方案。然而，原代 HAE 模型的最大缺点是其在培养中的有限增殖寿命。人们致力于了解体内和体外控制 HAE 细胞增殖和分化的因素。在这里，我总结了原代 HAE 培养的最新成就，特别强调了条件重编程细胞 (CRC) 的模型，该模型允许 HAE 细胞更长时间的体外增殖和分化。该综述比较了基于最近利用该模型发表的研究的 CRC HAE 技术变体（饲养细胞或 HAE 单细胞培养）。总结了每种 CRC HAE 模型变体的优缺点，并描述了影响 CRC HAE 培养成功的其他因素（组织类型、采样方法、样本质量）。
CRC HAE 培养物是呼吸研究中的一种有用技术，在许多情况下优于 iPSC 和类器官培养方法。在 iPSC 和类器官培养方法的当前局限性得到缓解之前，原代 CRC HAE 培养物可能是呼吸研究中的有用模型。气道上皮 (AE) 是一种覆盖人体气道全长的组织，从鼻子到支气管。AE 功能不当会导致几种人类气道疾病，例如哮喘、慢性阻塞性肺疾病 (COPD) 或囊性纤维化 (CF)。人们致力于寻找人类 AE 的最佳科学模型，以了解其在健康和疾病中的功能。在流行的 AE 模型中，有从人类供体中收集的原代体外培养的 AE 细胞。不幸的是，这种人类 AE (HAE) 细胞在体外不易分裂（扩增）；这对研究人员来说是一个巨大的后勤和伦理问题。在这里，我总结了人类 AE 细胞体外培养方法的最新成就，特别强调了条件重编程细胞 (CRC) 模型，该模型允许在体外更长时间、更有效地扩增原代人类 AE 细胞。该综述描述了 CRC 模型中使用的特定化学物质如何工作以允许增加 HAE 分裂，并比较了迄今为止开发的不同 CRC HAE 培养变体的效果。该综述还指出了需要改进的领域，以最大限度地提高来自人类供体的 CRC AE 培养物在人类气道疾病研究中的有用性。视频摘要。
