Developing non-animal ex vivo and in vitro models for studying arterial medial calcification
The Humane Research Trust is funding a research project to develop improved, non-animal models of arterial medial calcification. The scientists at the Royal Veterinary College will use human-derived tissue to study the mechanisms underlying the disease. This work will provide a platform for drug testing to replace the use of live animals and animal products.
Arterial medial calcification happens when bone-like deposits build up in a person’s arteries. This causes the arteries to stiffen, narrow, and carry less blood. The condition is common in older people as well as those with diabetes or kidney disease, and can cause cardiovascular events like stroke and heart attacks. Unfortunately, its underlying causes are complicated and remain poorly understood.
The availability of adult human blood vessels and cells for research is limited. As a result, research into this disease relies heavily on animal models. These experiments often quickly reach suffering severity limits, and it is common for animals to be euthanised during the studies. As a result, scientists are investigating more humane alternative models that also produce more human-relevant scientific findings.
“Issues with current models mean that progress in finding new therapies has been slow. Promising results from laboratory research have not translated through to effective drugs.” says Dr Isabel Orriss, Senior Lecturer in Comparative Biomedical Sciences at the Royal Veterinary College. “There is a clear need for new, non-animal experimental approaches that we can use to replace the current methods.”
The Humane Research Trust is funding a research project at the Royal Veterinary College to develop a human model of arterial medial calcification. Led by Dr Orriss, the researchers plan to use arteries isolated from donated human umbilical cords to model the disease.
“Development and validation of an umbilical artery model would enable the study of specific pathways, processes or compounds in a whole tissue setting,” explains Dr Orriss. “This means we can make use of the scientific advantages of 3D ex vivo culture without the need to use animals.”
Dr Orriss and her research team will isolate aortic rings from donated human umbilical cord. They will then culture the rings in a medium of calcium and phosphate. This will induce the process of calcification, mimicking that seen in the arteries of patients with the condition. The researchers will then test for the relevant markers of the vascular changes that occur in real patients.
Additionally, the scientists plan to adapt and improve current cell-based approaches so they no longer require animal products. They will culture and calcify vascular smooth muscle cells (VSMCs), the main cell type driving the development of the disease. This means they can test non-animal derived tissue culture supplements in search of one that best supports cell survival.
They will validate their models by testing various drugs that inhibit calcification. They hope to show that the models can successfully reproduce results seen in other studies of these compounds. This would confirm that these non-animal models could replacing traditional pharmacological animal testing. Going forward, scientists could discover and test treatments for arterial medial calcification using entirely animal-free methods.
