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Wouldn’t it be great if our bodies were a bit more efficient at healing? We will probably never be like the limb-regrowing salamanders, but our inability to regenerate many of our tissues following injury or disease is far from ideal. Take coronary heart disease (CHD) for example: it’s the leading cause of death in the U.S., but presently we lack an effective way to regenerate new arteries in affected hearts. But a new study could be helping us towards that goal.
In a first-of-its-kind study, scientists from Stanford have tracked the path of a single cell in a developing heart and identified a type of heart cell that gives rise to those that make up coronary arteries, highlighting a potential therapeutic target for the regeneration of these blood vessels.
“We are the first to label single cells at the surface of the mammalian heart,” lead author Katharina Volz told IFLScience, “and we followed how they go into the heart to form coronary artery smooth muscle.”
This knowledge is important, because if researchers want to be able to regenerate lost or damaged heart tissue, then an essential prerequisite is an understanding of how cellular building blocks come together to form these arteries in the first place.
But the researchers weren’t working from a complete blank slate: It was already known that a type of cell called an epicardial cell ultimately ended up forming the smooth muscle that makes up the outer layer of the coronary arteries. As the embryonic heart develops, some of these progenitors need to migrate from the epicardium – the layer covering the cardiac muscle – into deeper layers of the heart wall before forming the cells that compose the coronary artery smooth muscle (caSMCs). The finer details of this process and the signals that control it, however, remained unclear.
The Stanford scientists, led by Professor Kristy Red-Horse, came up with a neat way to fill in these blanks: Using a special imaging technique, they were able to track the fate of developing mouse heart cells, all the while conserving complex structures because they didn’t need to section the heart first. After tagging single cells and following their journey, they were able to pinpoint not only the location but the timing at which caSMCs first appear, Volz told IFLScience.
Then, using a method called “clonal analysis,” Volz and her team were able to work backward and demonstrate that caSMCs originate from cells called pericytes, with a signaling protein called Notch3 responsible for this transition, or differentiation. “In particular, we found evidence that arterial blood flow-induced Notch signaling is the signal for pericyte to smooth muscle differentiation,” Volz notes.
That find was encouraging for the team, since pericytes aren’t only found during development and are actually present in the adult heart, indicating a possible future therapeutic avenue where they are used to trigger self-healing mechanisms. In the case of heart attack-inducing coronary artery blockages, smaller blood vessels usually form around the site as a detour for the blood, but unfortunately they only offer a limited blood supply to tissues. But if scientists can somehow coax pericytes into caSMCs and thus prompt the development of more robust arteries, the process of repair could possibly be improved.
This may offer benefits to other techniques currently under investigation, for example growing a replacement in the lab or transplanting cells. That’s because it’s difficult to keep the grafted cells or tissue alive in the recipient, and also to encourage correct integration and differentiation. That said, Volz acknowledges that they don’t yet know what signals would be needed to encourage caSMC formation, but hopefully future studies will shed light on this.
The findings of this study are published in the open-access journal eLife.
