Skin cells into stem cells for arrhythmia treatment
Chris Denning works out of a lab at the University of Nottingham, where he and his team are using innovative stem cell techniques to test the effectiveness of approved drugs on patients with long QT syndrome – a type of arrhythmia.
The syndrome is usually treated with beta-blockers, which can have some inconvenient side effects.
As always, new treatments are needed - but the process of clinical trials to find those new drugs is often long and involved.
Chris is helping narrow down the list of potential treatments, but in an unusual way. Instead of asking people to take pills or have injections, he’s taking their skin cells away to the lab.
Thanks to Nobel Prize winner Shinya Yamanaka’s work, those skin cells can then be turned into stem cells. The process is already so refined that it can take just 3 to 4 weeks to get those stem cells, and after a month or so to make sure everything is fine, they’re then given the boost that turns them into cardiomyocytes – heart cells.
Chris says, “For decades we scientists struggled with massively complex ways of turning one type of cell into another, usually starting with egg cells like the frogspawn John Gurdon created, and moving slowly forward into other areas with the technology that created medical marvels like Dolly the Sheep. But for every step forward there was another setback, and the ethical considerations were massive.
Chris tells us more about science's struggle with stem cells
“Without Yamanaka’s major discovery and the work of those who came before him, what we’re doing now would simply not be possible. In particular Jamie Thompson in the United States’ work on embryonic stem cells meant we started well ahead of the game.
“Yamanaka transformed the way we think about stem cells. Who would have thought that it only takes four genes to turn more or less any type of cell into a stem cell?”
And once they have stem cells, how do they turn them into heart cells? Chris says “We give them the same kind of signals Mother Nature gives us in the womb.”
It can take up to six months to generate enough heart muscle cells, but when they’re ready Professor Denning and his team can test all sorts of drugs with the potential to help patients with long QT right there in the lab.
“Finding out that we could take ordinary skin cells from someone with long QT, turn them into stem cells and then heart cells, and they still behaved the way they would for someone with the syndrome was a real breakthrough.
“Being able to test drugs on heart cells in a dish has made the process of discovering treatments so much more efficient.”
'I have to thank John Gurdon'
Dr Andreia Bernardo is working hard to learn more about how an embryo’s heart develops in the womb. In the future she hopes this will help lead to new treatments and techniques for diagnosing congenital heart disease.
But without access to stem cells, this kind of research would be almost impossible.
“With stem cells we can mimic the development of the heart and study what happens when, say, a particular protein isn’t present. We’re looking at a protein that appears to be key to ensuring the early heart develops properly,” explains Dr Bernardo.
Andreia divides her time between labs at the National Institute for Medical Research in London and the University of Cambridge, home of Nobel Prize winner John Gurdon whose pioneering research was the foundation for stem cell studies like hers.
“I have to thank him – his work completely changed the field of developmental biology and ultimately paved the way to deriving human embryonic stem cells without having to use human embryos.
"John Gurdon proved that specialised adult cells still contain the genetic information needed to become other types of adult cells. He created a whole new frog from a single adult cell taken from a frog’s intestine.”
Find out what happened when Andreia met her heroes
Being at Cambridge with John Gurdon and hearing him speak is a tremendous honour for Dr Bernardo – he still attends lab meetings, even on the day he won the Nobel Prize.
Shinya Yamanaka, who shares the Nobel Prize with Gurdon, was also an inspiration at a key point in Andreia’s scientific career. Yamanaka took Gurdon’s discovery further – he found a way to turn cells that couldn’t change into ones that could, - known as induced pluripotent stem (iPS) cells - without needing an egg cell.
“I was just finishing my PhD when he made his key stem cell discovery. In 2007, I went to one of his first talks after the research on human iPS cells was published. It was a really exciting time and I was fortunate enough to meet him – despite the magnitude of his findings, he was incredibly humble.”
“I’m now able to use stem cells as a tool to study questions about how the heart develops. Ultimately I hope this work will contribute to our understanding of congenital heart disease and contribute to new ways to treat it.”
We know who Andreia would thank if she wins a Nobel Prize one day. In the meantime we hope to see how her research progresses so that in the future, it can help babies born with heart defects.