DCU researchers have developed an artificial blood vessel which incorporates living tissues, pumps and plastic tubes, writes Dick Ahlstrom
Medicine meets engineering in the Vascular Health Research Centre at Dublin City University. It conducts cross-discipline research including the creation of a "bioartificial blood vessel" that combines living tissues and mechanical equipment.
The object is to study what happens to particular cells and tissues during the development of cardiovascular disease, explains Prof Paul Cahill, director of the centre. "The main thrust of the centre really is to find the causes of vascular problems that initiate vascular disease," he says.
Prof Cahill was recruited to DCU from the US. "The vascular expertise I had in the US came back with me to DCU." He formed the nucleus of the centre and was soon joined by exercise physiologist, Dr Niall Moyna, who also returned from the US. They in turn were joined by Dr Brian McNamara, a design engineer with industrial background in tissue replacement therapies.
This team began working on cardiovascular research with funding first from the Health Research Board and later Wellcome Trust and the Programme for Research in Third Level Institutions, cycle three, Prof Cahill says.
"One of our major targets is the lining inside the \ vessel, the vascular endothelium," he explains. It releases many substances "good and bad" as it responds to substances circulating in the blood, to changes in blood pressure and to the "sheer" forces caused by the flow of blood.
"We look at how the endothelium underlies the fate of cells associated with the vascular system," he says. "One of the hallmarks of vascular disease, which is the number one killer in Ireland and around the world, is endothelial disfunction. We can model that very nicely."
The question was how to study what the endothelium was doing and what factors affected its performance. The centre's answer was the development of the bioartificial blood vessel, a construct that includes endothelial cells, smooth muscle cells typical of those found in blood vessels and porous plastic fibres measuring just a half millimetre across.
These very narrow tubes are coated with a protein matrix onto which living cells can be encouraged to grow. A single layer of endothelial cells cover the entire inside surface of the fibres and smooth muscle cells are grown on the outside of the fibres.
Fifty fibres, measuring seven centimetres long, are bundled together into a single structure and these are connected to pumping systems that can force liquids through them. The system achieves a flow through rate of about 28 millilitres per minute.
This combination of cells, pumps and tubing provides a powerful model of how the vascular system works when under stress, explains Prof Cahill. The medium pumped through the system carries nutrients that feed the cells, with these substances passing through the endothelial cells via the porous fibres and into the smooth muscle cells. This approximates what happens in an actual blood vessel where muscle cells are perfused via the endothelial cells.
The pumping system delivers forces similar to those exerted by the heart in normal circulation. "Vascular endothelial cells are always being sheered and pulsed by the blood flow," says Cahill. "If you want to model the performance of these cells you have to look at the mechanical forces." Static cell cultures do not provide an accurate enough picture.
The model allows the research team to elevate pressures as would happen in hypertension or high blood pressure. They can vary the nutrient mix, for example pushing up glucose levels to mimic conditions similar to diabetes or increasing fatty acids to create a classic high cholesterol level.
The system can use cultured bovine, rat, mice or human cells as appropriate to the particular experiments. The object is to learn more about disease processes as a way of finding new ways to treat cardiovascular disease. "We are looking for major targets for intervention."
Experimental drugs can be applied to the system to see how they work for or against a disease status. The complex network of genes associated with these processes can also be studied, genes linked to all aspects of the vascular system. "We are learning more about these developmental genes," he says.
The team uses the bioartifical vessel to examine proteins and genes linked to cardiovascular disease. The techniques used might also find their way into a "novel bioartificial vessel implant device" applicable to heart transplant patients, he added. This approach would involve using the transplantee's own cells and act as a platform for vascular gene therapy to treat disease.