A new animal free alternative to study atherosclerosis

GENIUS and IN-CONTROL in transition; a novel ex-vivo based model system to study atherosclerosis

Arteriosclerosis or atherosclerosis, the main cause of cardiovascular disease, is a chronic inflammatory disease caused by the accumulation of inflammatory cells and cholesterol in the vessel wall. The atherosclerotic plaque created by this inflammatory response can grow in such a way that it can completely close the artery. In addition, the plaque can rupture and cause a blood clot, possibly resulting in a heart attack or stroke. Various organs in the body play a role in the development of atherosclerosis, so the underlying mechanisms of this disease are often investigated in laboratory animals. However, the data obtained from these studies cannot always be directly translated to humans.

In this project, the aim is to develop a new ex vivo model based on the atherosclerotic plaque from humans, in which candidate drugs that counteract atherosclerosis can be tested. Atherosclerotic plaque material from patients undergoing endarterectomy will be used to develop this model. The patients undergo this surgery to remove an advanced atherosclerotic plaque from the carotid artery, often when these patients have had a stroke. This plaque will be cut into slices, after which these slices will be placed in a culture dish.

In this project the optimal conditions to be able to culture these slices for as long as possible will be investigated, so that candidate drugs can be tested for them. In accordance with the goals set in the Transitie Proefdiervrij Innovation (TPI) initiative, this model will lead to a reduction in the number of laboratory animals used in cardiovascular research, and the results obtained from these studies will be directly translated to the patient. In addition, this model can be used to discover new biomarkers that can accelerate the transition from candidate drugs to clinical studies.

Atherosclerosis is the main underlying cause of cardiovascular disease (CVD) and due to its multifactorial natural is often studied in animal models. Here the aim is to develop an innovative ex vivo system to study the atherosclerotic disease process based on the actual human atherosclerotic plaque. In line with the Transition to Animal-free Innovation (TPI), the aim is to develop a model that generates data on the effect of novel drugs that is highly translatable to the effect of the novel drug in the cardiovascular patient, while at the same time minimising the number of laboratory animals used. Moreover, the aim is to utilise this model to discover new biomarkers of successful treatment, which could expedite the transition of CVD therapeutic into clinical trial.
Technology Readiness Level (TRL)
3 - 5
Time period
36 months