Iriondo Cinta, Koornneef Sem, Skarp Kari-Pekka, Buscop-van Kempen Marjon, Boerema-de Munck Anne, Rottier Robbert J
Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.
Department of Cell Biology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.
Int J Mol Sci. 2025 May 23;26(11):5027. doi: 10.3390/ijms26115027.
Current animal and in vitro cell culture models do not fully recapitulate the physiological and pathophysiological characteristics of the human lung. As a result, the translation of these models to clinical practice is very limited, and clinical trials initiated on the extrapolation of such data fail. Although current models are beneficial in fundamental research, there is a need to constantly improve models to more accurately predict outcomes in clinical trials and personalized medicine. Here, we report important strategies to develop a 3D lung model with human primary lung cells. Starting from the well-established air-liquid interface (ALI) culture system, we describe a gradual increase in the complexity of the system by co-culturing different primary cell types, by testing different coatings, and by adding a three-dimensional matrix. As a result, we have established a reproducible 3D in vitro model of the airway consisting of human primary cells representing a differentiated mucociliary airway epithelium, an underlying submucosa with fibroblasts, and an endothelial interface.
当前的动物和体外细胞培养模型不能完全重现人类肺部的生理和病理生理特征。因此，这些模型在临床实践中的转化非常有限，基于此类数据推断开展的临床试验也失败了。尽管当前模型在基础研究中有益，但仍需要不断改进模型，以更准确地预测临床试验和个性化医疗中的结果。在此，我们报告了利用人类原代肺细胞开发三维肺模型的重要策略。从成熟的气液界面（ALI）培养系统开始，我们描述了通过共培养不同原代细胞类型、测试不同涂层以及添加三维基质来逐步增加系统的复杂性。结果，我们建立了一种可重现的气道三维体外模型，该模型由代表分化的黏液纤毛气道上皮、含有成纤维细胞的下层黏膜下层以及内皮界面的人类原代细胞组成。
