ORGAN-ON-A-CHIP MODEL OF PULMONARY ARTERIAL CELL-CELL INTERACTIONS

肺中的血管调节血液进入氧气，它们的正常功能对维持生命很重要。由于动物生理与人类不同，没有良好的人体血管实验模型，影响肺血管的疾病无法治愈，因此新药在临床试验中失败。我们利用内皮细胞和平滑肌细胞两种细胞类型制作了人体小肺动脉器官芯片模型，引起了制药行业的兴趣。然而，血管中包含许多其他类型的细胞，它们相互作用来调节血管功能，模型需要改进，以更好地反映真实血管的生理，并允许观察血管生长或重塑等长期过程。我们的目标是通过引入其他肺血管细胞类型和优化设备来研究新血管形成和长时间观察细胞行为，从而提高我们模型的生理相关性。该项目如果成功，将为研究健康和疾病中的肺血管生理学提供新的途径，建立人类供体特异性模型，减少人类肺部疾病（如肺动脉高压、急性肺损伤或慢性阻塞性肺疾病）的动物模型。该设备易于制造，价格低廉，可扩展，对基础科学机构和制药行业都有好处。

Blood vessels in the lung regulate access of blood to oxygen and their proper function is important to sustain life. Diseases that affect lung blood vessels remain incurable because animal physiology is different from human and there are no good models of human blood vessels to experiment on so new drug candidates fail in clinical trials.We have made an organ-on-a-chip model of small human lung artery using 2 cell types, endothelial and smooth muscle cells which gained interest of pharmaceutical industry. However, blood vessels contain many other cell types which interact with each other to regulate blood vessel function and the model needs to be improved to better reflect physiology of a real blood vessel and allow observation of long-term processes such as blood vessel growth or remodelling. We aim to improve the physiological relevance of our model, by introducing other pulmonary vascular cell types and optimising the device for studying new blood vessel formation and observations of cell behaviour over longer periods of time. The project, if successful, will provide a new way of studying lung blood vessel physiology in health and disease, establish human donor-specific models and reduce animal modelling of human lung diseases such as pulmonary hypertension, acute lung injury or chronic obstructive pulmonary disease. The device can be easily made, is cheap and scalable and would be a benefit to basic science institutions as well as pharmaceutical industry.