Summary

Pulmonary hypertension (PH) is an incurable disease affecting 1% of world population, with life expectancy <3 years. It is caused by thickening of arteries in the lung. Animal models do not reflect the human disease so new models need to be created. Arteries consist of endothelial, smooth muscle cells and fibroblasts. In normal arteries, endothelial cells are aligned within the direction of flow, while smooth muscle cells wrap around the vessel at 90 degrees. It is important to re-create the 3-layer structure of the artery, as all three cell types contribute to the vascular remodelling in PH.

In the pulmonary artery-on-a-chip (PA-O-C), human blood vessel cells are cultured under flow in chambers corresponding to the size of human lung arteries affected by the disease (https://www.youtube.com/watch?v=dqniQfROc9A). This PDMS-based, transparent device allows monitoring cell proliferation and other responses using fluorescent assays. To mimic the natural membrane that separates the two cell types, the BWS’ group have recently made a thin, porous PDMS membrane with improved optical and elastic properties. We propose to pattern adhesive proteins on PDMS to encourage smooth muscle cell alignment, and to complete the 3 cell- type model by introducing a hydrogel-based 3D layer of adventitial fibroblasts.

This project will involve an exchange of two PhD students between laboratories to facilitate development of the device: first, the student from ICL will learn from VP’s group micropatterning and 3D hydrogel culture, and will test in Leeds properties of the optimized porous membrane. In London, the student from Leeds will complete the PA-O-C by including primary blood-outgrowth endothelial cells from PH patients that can specifically replicate disease responses and serve as surrogates for patient lung cells in the device.
Expected outcome: a functional PA-O-C, with correct alignment and growth of 3 cell types, capable of supporting growth of blood-derived patient cells.