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

肺中的血管调节血液与氧气的接触，它们的正常功能对维持生命很重要。影响肺血管的疾病仍然无法治愈，因为动物生理学不同于人类，并且没有良好的人体血管模型进行实验，因此新的候选药物在临床试验中失败。我们使用2种细胞类型（内皮细胞和平滑肌细胞）制作了人肺小动脉的器官芯片模型，引起了制药业的兴趣。然而，血管包含许多其他细胞类型，它们彼此相互作用以调节血管功能，并且模型需要改进以更好地反映真实的血管的生理学，并允许观察长期过程，例如血管生长或重塑。我们的目标是通过引入其他肺血管细胞类型并优化研究新血管形成和观察细胞行为的设备，来提高我们模型的生理相关性。该项目如果成功，将提供一种研究健康和疾病中肺血管生理学的新方法，建立人类供体特异性模型，减少肺动脉高压、急性肺损伤或慢性阻塞性肺病等人类肺部疾病的动物模型。该装置易于制造，价格低廉，可扩展，对基础科学机构和制药业都有好处。

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.