Construction of an immuno-competent and self reporting human lung model using nanosensor incorporated scaffolds

人类肺部生物学的研究对我们理解哮喘、囊性纤维化和慢性阻塞性肺疾病(COPD)等具有重大健康和社会经济意义的疾病的疾病过程有着巨大的影响。目前，很难在人类身上进行这样的研究，因为在许多情况下，这不是安全的，或者程序过于侵入性，使用动物模型并不总是合适的。例如，小鼠不会自然患上哮喘，这表明它们的肺部生物学与人类不同。因此，生理上相关的人类肺模型的这些局限性将继续对寻找治疗干预的新靶点和分子产生负面连锁反应。例如，尽管加强了病人护理，哮喘的发病率和死亡率仍然居高不下，仅在英国，每19分钟就有一人死于哮喘，每年损失2000万个工作日。这在一定程度上是由于缺乏有效的治疗策略，以及很大一部分患者对治疗没有反应。在这个项目中，我们想要做的是在实验室里利用之前从捐赠的组织或血液中分离出来的细胞来开发一个人类肺的模型。我们将在含有传感器的材料上培养这些细胞，这些传感器可以捕捉氧气、葡萄糖和酸度等方面的变化。这些传感器将使我们能够实时观察细胞对刺激的反应。通过在这些材料上培养这些细胞类型，我们可以将它们排列成几层，这样细胞就可以在实验室中以与肺中相同的位置生长。这样的模型将为科学家和制药公司提供一个更好的工具，用于研究人类肺部生物学的某些方面，识别治疗的新靶点，并测试新的药物化合物。

The study of human lung biology has a huge impact on our understanding of the disease process in a number of lung conditions such as asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD), disorders which have significant health and socioeconomic implications worldwide. At the moment, it is difficult to carry out such research on humans, because in many cases it is not safe or procedures are too invasive, and the use of animal models is not always appropriate. For instance, mice do not develop asthma naturally which suggest that the biology of their lungs is different to that of humans. These limitations in the availability of physiologically relevant human lung models are therefore set to continue having a negative knock-on effect on the search for novel targets and molecules for therapeutic interventions. For example, despite enhanced patient care, the morbidity and mortality of asthma has remained high with one asthma related death every 19 minutes and 20 million lost working days per annum in the UK alone. This is partly due to lack of efficient therapeutic strategies and the fact that a large proportion of patients do not respond to treatment. What we want to do in this project is to develop a model of the human lung in the laboratory using cells previously isolated from donated tissue or blood. We will grow these cells on materials that contain sensors that can pick up changes in, for example, oxygen, glucose and acidity. These sensors will allow us to observe how cells respond to stimulation in real time. By growing these cell types on these materials, we can arrange them into layers such that the cells are grown in the laboratory in the same position as in the lung. Such a model would give scientists and pharmaceutical companies a better tool for investigating some aspects of human lung biology, identifying new targets for treatment and testing new drug compounds.