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Defining a xeno-free, human iPSC-derived 3D biomimetic vessel platform for the elucidation of mechanisms that drive vascular remodelling in pulmonary arterial hypertension
The Humane Research Trust is funding a research project to develop a better human model of pulmonary arterial hypertension. Researchers at the University of East Anglia are using cutting-edge technology to recreate pulmonary arteries in the lab. This piece of research will help us find potential treatments for the condition, as well as other vascular diseases.
Pulmonary arterial hypertension (PAH) is a fatal vascular disease, affecting both humans and animals. It is one type of pulmonary hypertension, in which narrow blood vessels result in high blood pressure. PAH affects the pulmonary arteries, which are the arteries in the lungs and the right side of the heart.
Unfortunately, the only cure for PAH is lung transplantation. In addition, patients do not begin showing symptoms until the disease has progressed significantly. This means that diagnosis often occurs too late. “Although existing therapies improve exercise capacity in patients, they have little impact on mortality,” said Dr Amer Rana, Associate Professor in Biomedicine at the University of East Anglia. “Consequently, there is a major unmet clinical need to develop new transformative therapies.”
Research into vascular diseases such as PAH often makes use of small animal models. However, these do not accurately recreate human disease. In particular, they fail to capture the small changes in the small pulmonary vessels, characteristic of PAH. In addition, vascular cells from real patients are only available at the point of lung transplantation or death. As such, these cells only represent the latter stages of the disease. This means scientists can't use this method to understand early disease progression.
Previous vascular research has shed light on the genetic mutations that may cause conditions such as PAH. However, we still don’t know enough about the environmental factors that can also contribute to the disease manifesting. The Humane Research Trust is currently funding Dr Rama to lead a research project into PAH. The research team is currently using human models of pulmonary vascular cells. Through this research, they hope to enhance understanding of the disease, alongside other vascular conditions.
Dr Rama and his research group have developed genetic stem cell models of human pulmonary vascular cells. They are able to transition the cells between disease-free and diseased states to investigate the processes that underly disease progression.
The researchers are using an innovative three-dimensional system to build functional human blood vessels in the lab. These 'biomimetic vessels' can effectively model pulmonary arteries. The scientists apply a system called ‘microfluidics’ to the vessels. This enables them to change the flow of blood or the amount of oxygen, and monitor the impact.
“This system allows us to model very closely what happens in disease in a way that researchers in the field have never been able to do before,” said Dr Rama. “This will represent a change in PAH research and has major advantages over the use of current animal models.”
The Humane Research Trust is delighted to be supporting this ground-breaking research project. We hope that this model will help identify novel druggable pathways, leading to more effective treatments. The model has further applications in vascular research, too. Scientists could apply the model to coronary vessels to help them understand conditions such as atherosclerosis, heart disease and strokes.
