Stem Cells: The Heart of the Matter

By Ralph Birch

A team of researchers from Pennsylvania State University has developed a process that turns human stem cells into epicardium cells, the fibrous layer of heart tissue that surrounds the myocardium.

This method of generating epicardium cells could be useful in a variety of clinical applications, specifically for patients who suffer heart attacks. According to the Centers for Disease Control and Prevention, someone in the United States has a heart attack every 43 seconds.

“Heart attacks occur due to blockage of blood vessels,” said Xioajun Lance Lian, assistant professor of biomedical engineering and biology at Penn State and the leader of the study. “This blockage stops nutrients and oxygen from reaching the heart muscle, and muscle cells die. These muscle cells cannot regenerate themselves, so there is permanent damage, which can cause additional problems. These epicardium cells could be transplanted to the patient and potentially repair the damaged region.” 

Choosing the Right Pathway

In 2012, Penn State researchers found that if they treated human stem cells with chemicals that sequentially 

activate and inhibit a cell’s Wnt pathway, they become myocardium (or heart muscle) cells, which are responsible for pumping blood through the body.

Wnt signaling pathways are made up of proteins that pass signals into a cell using surface receptors. Researchers were aware of the need for additional information to be passed through the Wnt pathways for the stem cells to become epicardium cells, but the exact nature of that additional information wasn’t immediately clear.

 “We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didn’t know what that information was,” Lian said. “Now, we know that if we activate the cells’ Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells.” 

Sustaining Success

For the purposes of their study, researchers engineered the human stem cells to be reporter cells, which means they expressed a fluorescent protein once they transformed into epicardium cells. 

Researchers also found that they could keep the cells proliferating in the lab by treating them with a cell-signaling pathway Transforming Growth Factor Beta (TGF-β) inhibitor.

After 50 days, the cells treated with the TGF-β inhibitor did not show any signs of decreased proliferation. The control cells in the study — which were not treated with the TGF-β inhibitor — started to plateau after just 10 days.

The results of the Penn State study, which were published in a recent issue of Nature Biomedical Engineering, bring the research team that much closer to regenerating all of the different types of heart tissue using nothing but stem cells. Using stem cells to recreate the endocardium (the inner layer of the heart) is the next major hurdle that the research team is hoping to clear.

“We are making progress on that inner layer, which will allow us to regenerate an entire heart wall that can be used in tissue engineering for cardiac therapy,” Lian said.