21EBTA. Bioengineering iLUNGs - Building scalable, integrated, multicellular and personalised human in vitro LUNGs

人体呼吸系统的存在是为了进行气体交换，从而维持生命。肺的整个细胞表面是连续的，空气从主气道到树状的分支气道和气体交换发生的囊——这些被称为肺泡。尽管在肺各个部分的实验室模型方面已经取得了很大的进展，但它们不具有从气道到肺泡的功能进化的特征。综合模型的缺乏阻碍了理解肺生理学和肺部疾病发生的进展。此外，关键的社会问题，如开发针对特定疾病的新的吸入疗法，以及了解环境污染对肺部的影响，将通过更好的模型得到真正的改善。在这个项目中，我们的目标是设计一个人类肺的活模型，其中气道到肺泡囊是完全连接和功能。我们称之为iLUNG。我们工作的一个关键优势是，我们将使用来自单个患者的多种细胞类型来创建它们。这意味着它们将是真正个性化的“迷你肺”，因此有望反映出与我们培养细胞的人相关的疾病。这为更有针对性地治疗肺部疾病提供了可能，也为了解基本的肺生物学以及肺中不同类型的细胞如何相互交流提供了新的可能性。为了这个项目，我们组建了一个伟大的肺生物工程师团队，拥有工程和科学基础设施，并能接触到患者，使这个项目得以实现。我们对iLUNG的潜力感到非常兴奋，并完全有动力培养下一代肺生物工程师。最后，我们很清楚，我们希望这项技术在学术界和工业界得到广泛应用，并最终取得科学和商业上的成功。

The human respiratory system exists to perform gas exchange and thus support life. The entire cellular surface of the lung is continuous with air from the main airways, to tree-like branched airways and the sacs where gas exchange happens - these are called alveoli. Although there has been great progress in laboratory models of individual parts of the lung, they do not have this feature of functional evolution from the airways to the the alveoli. The absence of integrated models has hampered progress in understanding lung physiology and what happens in lung disease. Further, key societal issues like the development of new inhaled treatments for specific diseases and an understanding of what environmental pollution does to the lung would be really enhanced by better models. In this project, we aim to engineer a living model of the human lung where the airway to the alveolar sacs are fully connected and functional. We call it the iLUNG. A key advantage of our work is that we will use multiple cell types from an individual patient to create them. This means that they will be truly individualised "mini-lungs" and will therefore hopefully reflect the disease associated with the person that we grew the cells from. This opens up the possibility of more targeted treatments for lung disease as well new possibilities to understand basic lung biology and how different types of cells in the lung talk to each other.We have put together a great team of lung bioengineers for this proposal and have the engineering and scientific infrastructure as well as access to patients to make this project deliverable. We are tremendously excited by the potential of the iLUNG and are fully motivated to train the next generation of lung bioengineers. Finally we are clear that we want this technology to be used widely in academia and industry and eventually be both a scientific and commercial success.