Researchers developing specialized muscle cells from stem cells
Scientists at the Morgridge Institute for Research in Madison are getting closer to being able to create an artery bank, which would serve the same role as blood banks.
In a recently published scientific paper, the Thomson Lab -- led by renowned biologist Jamie Thomson -- spotlighted a new method for growing smooth muscle cells from stem cells that presents fewer complications than other methods.
Thomson made history when he isolated the first human embryonic stem cell in 1998. Now, more than two decades later, researchers in his lab are relying on stem cells as they work toward creating transplantable arteries.
According to Thomson, the researchers in his lab decided to focus on blood vessels, because cardiovascular disease is a major cause of death worldwide. It’s also the top cause of death in Wisconsin, a recent state report shows.
“And this work also has implications beyond making vessels for transplantation; it's sort of a stepping stone to more advanced tissue engineering,” he said.
Creating arteries in a laboratory setting requires two types of cells: smooth muscle cells, which drive organ function and other internal movements such as swallowing; and endothelial cells, which line the interior of blood vessels.
In 2017, the lab identified methods for creating endothelial cells, while the latest research published last week in the journal Stem Cell Reports focuses on smooth muscle cells. The study also points to a potential drug that could reduce risk for patients who’ve undergone bypass surgery.
Other researchers have produced smooth muscle cells from stem cells, according to lead author and Morgridge associate scientist Jue Zhang. But he says commonly used growth factors can lead to a condition called intimal hyperplasia, which can cause bypass tissue grafts to fail.
Intimal hyperplasia is characterized by a portion of the arterial wall thickening due to growing smooth muscle cells, which can cause blood vessels to narrow. The new research was prompted in part by a desire to reduce the risk of that condition occurring, according to Zhang.
"It's a common problem in smooth muscle cell differentiation, and if you want to make a useful artery, you don't want that risk,” Zhang said.
After screening more than 4,000 small molecules, his team identified a growth factor known as RepSox that had “the best potential” to produce cells that can contract without risking intimal hyperplasia. According to a release, RepSox is more stable than other growth factors and also costs less.
"Even after you have a bypass surgery, you can have some problems with your artery, like restenosis (narrowing arteries) due to intimal hyperplasia," Zhang said. "Currently there are only two FDA-approved drugs on the market [to address these problems], and they're not cell-type specific, meaning they have side effects. We found that RepSox inhibits intimal hyperplasia and has fewer side effects."
Zhang says the latest study moves the field closer to improving treatments for cardiovascular disease, but scientists are still grappling with the challenge of cell maturity.
"Basically this cell type is better than previous efforts, but it's still not mature yet," Zhang says. "We need to induce these cells to become more mature, to be more similar to our native artery, to make it more functional."
See more on the work being done in the Thomson lab at UW-Madison: http://morgridge.org/research/regenerative-biology/thomson-lab/