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

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.

The lack of vascular models of is a key obstacle to clinical translation. We have created a microfluidic model of a pulmonary artery, the (PA)-on-a-chip, that facilitates analysis of functional and transcriptional changes in human pulmonary arterial endothelial and smooth muscle cells exposed to various stimuli, responsible for the regulation of pulmonary vascular function. The model has attracted interest of pharmaceutical industry but the current design has a limited capacity for mimicking multicellular tissue environment, does not allow analysis of cell migration and angiogenesis and has only been used for monitoring short term cell responses.
We aim to improve physiological relevance of this model, by introducing design improvements that incorporate other pulmonary vascular cell types and further optimising the device for long term culture, which is necessary to observe processes such as angiogenesis and vascular remodelling.
The project, if successful, will help create a new platform for studying physiological and pathological vascular cell responses using human material and therefore help reduce animal experimentation in pre-clinical modelling of lung diseases. The device can be used for studying donor-specific responses, capturing specific molecular or genetic alterations. The device can be cheaply made, on a large scale and in a reproducible manner and would be a benefit to basic science institutions as well as pharmaceutical industry.