Modelling vascular pathology in pulmonary arterial hypertension in the pulmonary artery-on-a-chip

Pulmonary arterial hypertension (PAH) is a debilitating disease for which currently there is no cure. It has a poor prognosis with a three-year survival rate of 58.2% and a high mortality rate due to right heart failure, and an estimated prevalence of 12-15 per million. Currently, much of the information on vascular pathology in PAH is derived mainly from histological analyses of lung tissues and does not allow for real-time monitoring of cell responses.

Organ-on-a-chip technology uses transparent, micro-scale fluidic channels to recreate the tissue-tissue interfaces within organs. We have designed the pulmonary artery-on-a-chip, a polydimethylsiloxane (PDMS)-based model of the pulmonary vascular wall where human pulmonary artery endothelial cells (HPAEC) and human pulmonary artery smooth muscle cells (HPASMC) are co-cultured under haemodynamic conditions in chambers corresponding to the size of the affected human peripheral lung arterioles.

The pulmonary artery-on-a-chip aims to provide useful insights as to the effects of factors involved in the PAH pathogenesis on endothelial barrier dysfunction, endothelial-to-smooth muscle signalling and vascular remodelling in an in vitro environment that is more representative of in vivo conditions. The potential of organ-on-a-chip technology includes the reduction of animal experimentation, use in personalised medicine and the acceleration and cost reduction of drug development and validation.

Mini-bio

• PhD in Medicine (Current) Imperial College London
• MRes Cardiovascular and Respiratory Medicine (2018)  Imperial College London. Recipient of the Dean’s prize for Cardiovascular and Respiratory Medicine.
• MSc Molecular Medicine (2015) Imperial College London
• BSc Biomedical Science (2014) University of Hull

Publications

• Aldabbous, L., Abdul-Salam, V., McKinnon, T., Duluc, L., Pepke-Zaba, J., Southwood, M., Ainscough, A., Hadinnapola, C., Wilkins, M., Toshner, M. and Wojciak-Stothard, B. (2016). Neutrophil Extracellular Traps Promote Angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 36(10), pp.2078-2087.
• Nadappuram, B., Cadinu, P., Barik, A., Ainscough, A., Devine, M., Kang, M., Gonzalez-Garcia, J., Kittler, J., Willison, K., Vilar, R., Actis, P., Wojciak-Stothard, B., Oh, S., Ivanov, A. and Edel, J. (2018). Nanoscale tweezers for single-cell biopsies. Nature Nanotechnology.