A multidisciplinary team of researchers have discovered that stem cells can be used to generate epicardium cells – the cells that cover the external surface of the heart.
Unlike many other tissues in the body, heart tissue does not regenerate. The damage caused by a heart attack is repaired, but scar tissue forms – not healthy heart tissue. The researchers are hopeful that the generated cells could be transplanted into patients to help repair heart damage caused by a heart attack.
The research team has previously been successful in generating myocardium cells. The myocardium is the middle part of the heart’s three layers and is responsible for the contractions that pump blood through the body. Back in 2012, the team discovered that they could generate myocardium cells from human stem cells.
Lead researcher at Penn State University, Xiaojun Lance Lian, said “we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit Wnt signaling pathway, they become myocardium muscle cells.”
The Wnt signaling pathway involves Wnt proteins, which bind to cell-surface receptors to send signals inside cells. While the team was able to generate myocardium cells, in order to generate epicardium cells, it would be necessary to provide cardiac progenitor cells with the relevant signals. However, prior to the study it was not known what those signals were.
Lian explained that the study showed it was possible to generate epicardium cells rather than myocardium cells. “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.”
The team engineered stem cells to fluoresce when they developed into epicardium cells. An analysis of the generated epicardium cells showed they were similar to those found in living humans.
The team discovered that the generated epicardium cells proliferated in the lab, but plateaued after 10 days. However, when the researchers treated the cells with a cell-signaling pathway Transforming Growth Factor Beta (TGF) inhibitor, proliferation continued. There was no sign of a decrease in proliferation after 50 days.
The team has now successfully generated cells from the outer and middle layers of the heart. Now attention is focused on developing endocardium cells – the cells that line the inner surface of the heart. According to Lian, “We are making progress on that inner layer.”
If the team is successful, it will be possible to generate all three layers of the heart. That would allow the researchers to generate an entire heart wall that could be used in cardiac therapy
The research has recently been published in the journal, Nature Biomedical Engineering.