Stem cells could provide a treatment for a 'broken heart'

"Scientists believe they may have discovered how to mend broken hearts," reports the Daily Mirror.

While it may sound like the subject of a decidedly odd country and western song, the headline actually refers to damage to the heart muscle.

A heart attack occurs when the muscle of the heart becomes starved of oxygen causing it to be damaged. If there is significant damage the heart can become weakened and unable to effectively pump blood around the body. This is known as heart failure and can cause symptoms such as shortness of breath and fatigue.

The heart contains "dormant" stem cells, and researchers want to learn more about them to work out ways to get them to help repair damaged heart tissue.

In this new laboratory and animal study, researchers identified a characteristic genetic "signature" of adult mouse heart stem cells. This led to them being more easily identified than they have been previously, making them easier to "harvest" for study.

Injections of these cells into damaged mouse hearts was shown to improve heart function, even though very few of the donor cells remained in the heart.

These findings will help researchers to study these cells better, for example investigating whether they could be chemically triggered to repair the heart without removing them first. While the hope is that this research could lead to treatments for human heart damage, as yet the results are just in mice.

The researchers also note that they need to find out whether human hearts have the equivalent cells.

Where did the story come from?

The study was carried out by researchers from Imperial College London and other UK and US universities. It was funded by the British Heart Foundation, European Commission, European Research Council and the Medical Research Council, with some of the researchers additionally supported by the UK National Heart and Lung Institute Foundation and Banyu Life Science Foundation International.

The study was published in the peer-reviewed scientific journal Nature Communications. It is open access, meaning it can be read for free online.

The Mirror’s main report covers the story reasonably, but one of its subheadings – that scientists have identified a protein that if injected can stimulate heart cell regeneration – is not quite right. The researchers have not yet been able to utilise a protein to stimulate heart regeneration. They have just used a specific protein on the surface of the stem cells to identify the cells. So it was the cells, and not the protein, that were used in regeneration.

The Daily Telegraph’s coverage of the study is good and includes some useful quotes from the lead researcher Professor Michael Schneider. The article also makes it clear that this study only involved mice.

What kind of research was this?

This was laboratory and animal research studying the adult stem cells in mice that can develop into heart cells.

A number of diseases cause (or are caused by) damage to the heart. For example, heart attacks occur when some heart muscle cells do not get enough oxygen and die – usually due to a blockage in the coronary arteries that supply the heart muscle with oxygen-rich blood. There are "dormant" stem cells in the adult heart that can generate new heart muscle cells, but are not active enough to completely repair damage.

Researchers are starting to test ways to encourage the stem cells to repair heart damage fully. In this study, the researchers were studying these cells very closely, to understand whether all heart stem cells are the same, or whether there are different types and what they do. This information could help them to identify the right type of cells and conditions they need to fix heart damage.

This type of research is a common early step in understanding how the biology of different organs works, with the aim of eventually being able to develop new treatments for human diseases. Much of human and animal biology is very similar, but there can be differences. Once researchers have developed a good idea of how the biology works in animals, they will then carry out experiments to check to what extent this applies to humans.

What did the research involve?

The researchers obtained stem cells from adult mouse hearts and studied their gene activity patterns. They then went on to study which of these cell types could develop into heart muscle cells in the lab, and which could successfully produce heart muscle cells that could integrate into the heart muscle of living mice.

The researchers started by identifying a population of adult mouse heart cells that is known to contain stem cells. They separated out these into different groups, some of which are known to contain stem cells, and further separated each group into single cells, and studied exactly which genes were active in each cell. They looked at whether the cells showed very similar gene activity patterns (suggesting that they were all the same type of cells, doing the same things), or whether there were groups of cells with different gene activity patterns. They also compared these activity patterns to young heart muscle cells from newborn mice.

Once they identified a group of cells that looked like the cells that could develop into heart muscle cells, they tested whether they would be able to grow and maintain these in the lab. They also injected the cells into the damaged hearts of mice to see if they formed new heart muscle cells. They also carried out various other experiments to further characterise the cells that form new heart muscle cells.

What were the basic results?

The researchers found distinct groups of cells with different gene activity patterns. One particular group of these cells was identified as the cells that have started to develop into heart muscle cells. These cells were referred to as Sca1+ SP cells, and one of the genes they expressed produces a protein called PDGFRα, which is found on the surface of these cells. These cells grew and divided well in the lab, and the offspring cells maintained the characteristics of the original Sca1+ SP cells.

When the researchers injected samples of the offspring cells into damaged mouse hearts, they found that between 1% and 8% of the cells remained in the heart muscle tissue the day after the injection. Over time, most of these cells were lost from the heart muscle, but some remained (about 0.1% to 0.5% at two weeks).

By two weeks, some (10%) of the remaining cells were showing signs of developing into immature muscle cells. At 12 weeks, more of the remaining cells (50%) were showing signs of being muscle cells. These cells were also showing signs of being more developed and forming muscle tissue. However, there were only a few of these donor cells in each heart (5 to 10 cells). Some of the donor cells also appeared to have developed into the two sorts of cells found in blood vessels.

Mice whose hearts had been injected with the donor cells showed better heart function at 12 weeks than those who had a "dummy" injection with no cells. The size of the damaged area was smaller in those with donor cell injections, and the heart was able to pump more blood.

Further experiments showed the researchers that they could identify and separate out the cells that specifically develop into heart muscle cells by looking for the PDGFRα protein on their surface. The cells identified in this way grew well in the lab, and when injected into the heart they could integrate into the heart muscle and showed signs of developing into muscle cells after two weeks.

How did the researchers interpret the results?

The researchers concluded that they had developed a way to identify and separate out a specific subset of adult mouse heart stem cells and can generate new heart muscle cells. They say that at the very least this will help them to study these cells in mice more easily. If a human equivalent of these cells exists, they may also be able to utilise this knowledge to obtain stem cells from adult heart tissue.

Conclusion

This laboratory and animal study has identified a characteristic genetic "signature" of adult mouse heart stem cells. This has allowed them to be more easily identified than they have been previously. Injections of these cells have also been shown to be able to improve heart function after heart muscle damage in mice.

These findings will help researchers to study these cells more closely in the lab and investigate how they can prompt them to repair damaged heart muscle, possibly without removing them from the heart first. While the hope is that this research could lead to treatments for human heart damage, for example after a heart attack, as yet the results are just in mice. The researchers themselves note that they now need to find out whether human hearts have the equivalent cells.

Many researchers are working on the potential uses of stem cells to repair and damage human tissue, and studies such as this are important parts in this process.