University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Eur Respir Rev. 2023 Jul 26;32(169). doi: 10.1183/16000617.0042-2023. Print 2023 Sep 30.
Chronic lung diseases result from alteration and/or destruction of lung tissue, inevitably causing decreased breathing capacity and quality of life for patients. While animal models have paved the way for our understanding of pathobiology and the development of therapeutic strategies for disease management, their translational capacity is limited. There is, therefore, a well-recognised need for innovative models to reflect chronic lung diseases, which will facilitate mechanism investigation and the advancement of new treatment strategies. In the last decades, lungs have been modelled in healthy and diseased conditions using precision-cut lung slices, organoids, extracellular matrix-derived hydrogels and lung-on-chip systems. These three-dimensional models together provide a wide spectrum of applicability and mimicry of the lung microenvironment. While each system has its own limitations, their advantages over traditional two-dimensional culture systems, or even over animal models, increases the value of models. Generating new and advanced models with increased translational capacity will not only benefit our understanding of the pathobiology of lung diseases but should also shorten the timelines required for discovery and generation of new therapeutics. This article summarises and provides an outline of the European Respiratory Society research seminar "Innovative 3D models for understanding mechanisms underlying lung diseases: powerful tools for translational research", held in Lisbon, Portugal, in April 2022. Current models developed for recapitulating healthy and diseased lungs are outlined and discussed with respect to the challenges associated with them, efforts to develop best practices for model generation, characterisation and utilisation of models and state-of-the-art translational potential.
慢性肺部疾病是由肺部组织的改变和/或破坏引起的,不可避免地会导致患者呼吸能力和生活质量下降。虽然动物模型为我们理解疾病的病理生物学和开发疾病管理的治疗策略铺平了道路,但它们的转化能力有限。因此,需要创新的模型来反映慢性肺部疾病,这将有助于机制研究和新治疗策略的推进,这一点已经得到了广泛的认可。在过去的几十年中,人们使用精密切割肺切片、类器官、细胞外基质衍生的水凝胶和肺芯片系统,在健康和患病条件下对肺部进行建模。这三种三维模型共同提供了广泛的适用性,并模拟了肺部微环境。虽然每个系统都有其自身的局限性,但与传统的二维培养系统相比,甚至与动物模型相比,它们具有优势,增加了模型的价值。生成具有更高转化能力的新型先进模型不仅将有助于我们理解肺部疾病的病理生物学,还应该缩短发现和生成新治疗方法所需的时间。本文总结并概述了 2022 年 4 月在葡萄牙里斯本举行的欧洲呼吸学会研究研讨会“用于理解肺部疾病机制的创新 3D 模型:转化研究的有力工具”的内容。本文概述并讨论了目前为再现健康和患病肺部而开发的模型,以及它们所面临的挑战、为模型生成、表征和利用制定最佳实践的努力,以及最先进的转化潜力。