People suffering from a wide range of health problems need vascular transplants — replacing damaged arteries and veins. Cardiovascular disease accounts for one in every three deaths each year in the United States, more than all forms of cancer combined.
At the Morgridge Institute, stem cell pioneer James Thomson is leading a potentially transformational project to develop a safe and functional cell-based artificial artery that could be pulled from medical inventories and used by vascular surgeons.
“People with diabetes and sclerosis frequently suffer from blockage in the main arteries in their legs, a debilitating condition that often leads to amputation and even death,” says Thomson. “So far, we have used artificial grafts made of synthetic materials. But as the grafts get smaller and smaller, they fail at a higher and higher rate. And for smaller arteries like in the heart, they aren’t used at all.”
Producing arteries in the lab requires two essential cell types: endothelial cells, which line the interior of blood vessels, and smooth muscle cells from pluripotent stem cells, Thomson says. In 2017, the Thomson Lab was able to generate and characterize endothelial cells. Now, its latest research focuses on the smooth muscle cells. Healthy smooth muscle cells need the ability to contract so they can distribute blood throughout the body and regulate blood pressure.
“We are now seeing some hopeful results with peripheral artery disease.”James Thomson
The lab is developing scaffolds from natural and synthetic materials to provide structure and shape for the artery. UW–Madison biomedical engineer Naomi Chesler is working on a bioreactor that provides an environment in which the arterial cells can grow around the scaffolding.
“There are still challenges, such as the body rejecting artificial arteries, and there is also a risk of cancer, so we have a lot of work to do,” Thomson adds.
The lab has discovered a small molecule, known as RepSox, that has the best potential to produce cells with the properties that allow arteries to bend and stretch. The characteristics that make RepSox good for differentiating smooth muscle cells also make it a desirable drug candidate to reduce risk of post-surgery complications. “We are now seeing some hopeful results with peripheral artery disease,” Thomson says.
Thomson adds that there is similar work taking place in Europe where they remove a vein, culture the endothelial cells for about a month, and then line the artificial vessels and put them back in, and they work about as well as veins.
The lab is hoping to create tissue with cells banked from a unique population of people who have genetic characteristics that help circumvent rejection. It has been estimated that about 100 different cell lines from this rare population would be enough to cover a majority of the U.S. population.
“If we can replace those cells in a way that is tolerated, it’s probably going to work,” Thomson says. “My confidence level is very high.”