The Humane Research Trust is funding a research project to investigate the role of vascular dysfunction in heart failure. Using 3D cell culture models and advanced computer modelling, the University of Surrey researchers will simulate human blood vessels. This will shed light on the cellular behaviour underlying heart failure, laying the groundwork for finding new treatments.
Heart failure is an increasingly common condition, caused by a plethora of genetic, lifestyle and acute stressors. Over the past 20 years, heart failure research has come a long way, but we still lack adequate treatments. This is affecting patients' quality of life as well as putting strain on the UK’s healthcare system.
By analysing patient samples, scientists have developed several important insights into the disease. However, there is still a need to develop new, human-relevant models to test potential treatments. Scientists have historically modelled heart failure in small animals. These animals face harmful genetic modifications, invasive surgical procedures, and taxing long-term treatments.
“The increasing burden of heart failure highlights the poor translational and unethical nature of animal studies and the need for new approaches,” says Dr Paola Campagnolo, Senior Lecturer in Molecular Cardiovascular Sciences at the University of Surrey.
Recently, scientists discovered that dysfunction of the small blood vessels in the heart precedes the heart-muscle related symptoms. As a result, scientists think focusing on this vascular dysfunction could result in promising new interventions for heart failure patients.
The Humane Research Trust is funding a research project at the University of Surrey to investigate the role of vascular dysfunction in heart failure. The researchers, led by Dr Campagnolo, will combine a 3D culture model with innovative computer modelling techniques.
Dr Campagnolo’s 3D spheroid model mimics the composition of human capillaries, including organ-specific cells like the endothelial cells that line the inside of the blood vessel, and the pericytes that support the endothelial cells. These cell types are significant since they change their organisation as the disease progresses. As a result, their inclusion is integral in effectively modelling heart failure.
During this project, the scientists will simulate heart failure by subjecting the vascular spheroids to various environmental conditions. They will assess which conditions are successful in replicating vascular dysfunction, using advanced imaging techniques and gene expression analyses.
Then, they will use this data to produce a bespoke mathematical model that reproduces the spheroid digitally. This 'digital twin' will generate predictions of the potential mechanisms to explain the cell behaviour seen in heart failure. The scientists are hoping that these insights will enable their collaborators to begin testing new potential treatments.
“Developing a simple and transferrable 3D in vitro model in combination with a digital twin technology is a cost-effective and humane way to study the causative mechanisms of heart failure,” says principal investigator Dr Campagnolo. “This project will extend the ongoing work to address the challenges of this debilitating and complex disease.”
Dr Paola Campagnolo
Principal investigator
Dr Paola Campagnolo is Lecturer of Molecular Cardiovascular Biology at the University of Surrey. Her laboratory focuses on developing in vitro and ex vivo 3D multicellular models to study cardiovascular physiology and disease. They use these approaches to reveal new insights into cardiovascular health, test novel therapeutics, and advance the field of regenerative medicine.
Rahme Nese Safakli
Postdoctoral researcher
Rahme is a Postdoctoral Research Associate at the University of Surrey. She recently completed her PhD in Cardiovascular Research at the university, in which she investigated how heart cells respond to stress by managing damaged proteins within their mitochondria. During this time, she developed her skills in using molecular and cellular biology techniques to study cardiovascular diseases.
