How stem cell research could help repair heart attack damage

Professor Ian Wilmut with Dolly

Stem cell research could reveal new ways to help us mend broken hearts, as Sarah Kidner discovers.

Chances are you’ve heard of stem cells. Even if you haven’t, you’ll know of Dolly the cloned sheep – the original ‘poster girl’ of this sensational field of scientific research.

Twenty years ago, Dolly’s creation saw scientists accused of ‘playing God’, but while stem cell research does raise ethical questions, it may also hold the key to mending hearts damaged by a heart attack and has many other potential uses.

It’s an amazing breakthrough

Professor Chris Denning

Two professors at the cutting edge of stem cell research tell us how their work could affect people’s lives in the future.

“Ten years ago, we couldn’t have conceived of these studies,” says Chris Denning, Professor of Stem Cell Biology at the University of Nottingham. “But what was once impossible is now possible.”

He’s referring to induced pluripotent stem (iPS) cells. Their development won Shinya Yamanaka and John Gurdon the Nobel Prize for Physiology or Medicine in 2012. But what are iPS cells, and why is this type of research such a big deal?

iPS cells explained

Until recently, to conduct stem cell research scientists needed to obtain human embryonic stem cells from spare IVF embryos with the consent of those involved. These embryonic cells could be coaxed into becoming any human body cell.

Research stats on stem cellsToday, you can simply take a skin biopsy or a blood sample from a patient, isolate skin or blood cells and, by adding four genes, convince them that they are stem cells.

“The gene cocktail used can differ, but the most common factors are called the Yamanaka factors, after Shinya Yamanaka, and are all stem cell-related genes,” explains Professor Denning. The beauty of the iPS cell technique lies in its simplicity.

“Everybody thought he [Yamanaka] was crazy when he presented iPS cells at one big international conference. Within a year several labs had repeated the technique. Yamanaka was a superstar; the Japanese government invested £65.1m in him. Just six years later, he won the Nobel Prize.”

Patient in a dish

Professor Chris DenningBy adding specific growth factors, you can turn iPS cells into beating heart cells in a dish. This means it’s possible to study people with heart conditions without conducting invasive procedures.

“Imagine you have an inherited heart condition,” says Professor Denning (pictured right). “I say: ‘I would like to investigate it using some of your heart cells, so I need to crack your chest open and cut out a little piece of your heart. But because the cells only last a few weeks in the lab, can I come back the next week and do the same again?’ It’s not going to happen.

“Now, I can take a skin biopsy, do the genetic programming that turns it into stem cells and keep growing them. We’re still working with the same population of cells we reprogrammed in 2008 and all we took was a skin biopsy the size of a matchstick head.”

Professor Denning uses iPS cells to research inherited conditions that lead to sudden death. “When patients with this condition get stressed or experience strange stimuli, they can start to experience terrible arrhythmias,” he explains.

We are reaping the harvest of several decades of painstaking research

BHF Professor Michael Schneider

“What we’re able to do in a lab is mimic the person’s condition in a culture dish. This is because the cells retain the genetic abnormalities present in those who donated the skin biopsy.”

New drug therapies to regenerate dead cells?

‘Patients in a dish’ could also help create new drugs. “If you’re a person with a condition and someone says they want to test 1,000 different drugs in you, you would say ‘I think not’ – some of them might be harmful,” says Professor Denning. “But if you can replicate these things, you can ask if those drugs work when tested in a dish.”

He says what makes this cutting-edge work worthwhile is seeing the impact it might have on people’s lives. “Once in a while, you have a little bit of a breakthrough, but I have to say that the thing that made me happiest was when we published our 2011 paper. Our clinical colleagues forwarded it on to a patient’s family and the father replied to thank us for the work we’re doing in this area. That is why we’re doing it.”

When someone suffers a heart attack, cells in the heart are starved of oxygen and die. This can lead to the chronic and life-limiting condition heart failure, for which there’s currently no cure.

BHF Professor Michael SchneiderWe don’t know how to mend or regenerate dead cells, but stem cell research could unlock new ways of doing precisely that.

BHF Professor Michael Schneider (pictured right) and his team at Imperial College London are leading research to explore how we can kick-start heart cells to regenerate or repair following a heart attack.

Their focus is on the limited number of stem cells, which already exist within the heart muscle, and to “learn how they might contribute to heart repair in the case of injury,” says Professor Schneider.

Specifically, the team aims to learn how the heart’s own stem cells become more effective at creating new heart muscle following a heart attack. “Our main emphasis is on finding highly cloneable cells with the ability to become all the needed cell types in the heart,” says Professor Schneider.

“It’s too early to say how this might work, but it may be that doctors deliver drug-like molecules or hormones into the body to activate stem cells in the heart to become new cardiac muscle. Or, they may be useful for cell grafting in the catheter lab, at the time of a heart attack or later on.”

Understanding of these techniques is continually growing. “There has never been a better time to support the BHF than now,” says Professor Schneider. “We are reaping the harvest of several decades of painstaking research and the advances and their progress into the clinic have never happened at a faster rate.”

Using stem cells in research

Analysing embryonic stem cells in the laboratoryThe BHF supports essential research using stem cells because we believe they have the potential to cure conditions that are incurable today.

We fund research that uses stem cells from human or animal embryos and adult tissues, because we believe that both approaches are important.

Many of the advances in stem cell research have only been possible through the knowledge and insight gained using embryonic stem cells. We recognise that this is an area some people have concerns about.

Embryonic stem cells

Embryonic stem cells used in research are donated by couples that have undergone in vitro fertilisation (IVF) treatment. They choose to donate spare embryos that would otherwise be destroyed, so that stem cells can be extracted for use in research. Only embryos at a very early stage of development (up to 14 days) can be used.

We’ll only fund research using embryonic stem cells where:

  • the application has been through a thorough scientific review panel, to which researchers must show that this project could not be carried out in another way
  • there is a licence from the Human Fertilisation and Embryology Authority
  • there is approval from an independent research ethics committee.

More work to be done

Heart and circulatory disease kills one in four people in the UK, but stem cell research holds real promise to help us save lives in the future.

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