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 pulmonary arteries in PAH.
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.