'Heart repair pill' still years away
“A drug that makes hearts repair themselves has been used in research on mice,” BBC News has reported.
The news is based on an early set of laboratory and animal experiments. Researchers identified cells in the outer layer of the heart that can develop into mature heart cells and replace injured heart tissue after being treated with a specific protein. These “progenitor cells” have the ability to develop into new heart muscle cells in embryos, but cannot normally do so in adults. However, researchers have found that dormant progenitor cells can be activated in adult mice by injecting them with a specific protein. When these mice were induced to have a heart attack, some of the treated progenitor cells developed into new heart muscle cells, integrating into the heart tissue and functioning as part of the organ.
This research is at a very early stage, and further studies on the effectiveness and safety of such treatment in animals will be needed before human studies can be carried out. In particular, if the biological mechanisms discovered also apply to humans, research will need to establish if the protein could have an effect if administered months or years before a heart attack, or even after one. This study mainly looked at administering the protein before heart damage occurred. Overall, despite the possibilities presented by this early research, a pill that can regenerate human hearts is still some years off.
Where did the story come from?
The study was carried out by researchers from University College London, Children’s Hospital Boston, Harvard Medical School, the Chinese Academy of Science and Imperial College London. It was funded by the British Heart Foundation.
The study was published in the peer-reviewed scientific journal_ Nature._
The findings of this study were mostly reported accurately by the media, with the BBC also accurately stating that potential treatment in humans is several years away. Several news sources discussed the experimental treatment as though it has already been developed into a pill suitable for use in humans. However, this process is likely to take many years.
What kind of research was this?
This laboratory and animal study investigated whether cells in the adult heart could be induced to make new heart muscle cells after injury. Previous studies have confirmed the existence of progenitor cells, which can make new heart muscle cells in the outer layer of embryonic hearts but not adult hearts.
Adult hearts that are damaged, for example by a heart attack, do not usually make new heart muscle tissue to repair the damage, which is currently considered to be permanent. If adult hearts could be induced to make new heart cells, it could potentially be a way to repair some of the tissue damage that occurs when someone’s heart is injured. Also, because these new cells would be generated by a person’s own body, they would not be treated as foreign bodies and rejected, as tissue transplanted from another individual would be.
Researchers first confirmed the presence of these cells in the outside layer of the heart in adult mice, then looked at whether they could induce the cells to develop into functional heart muscle cells. They also identified a marker that would allow them to monitor cell development and trace the cells throughout the study.
They then conducted a controlled experiment in mice to test how protein-induced cell activation affected the repair of damaged heart tissue. This included examining the development of progenitor cells into heart muscle cells, their movement to the site of injury, and their integration with functioning heart muscle cells.
Finally, researchers used scans to assess how the methods they had developed affected heart function and heart tissue repair in mice that had been induced to have a heart attack.
This type of animal research allows researchers to study cells and tissues in a way that would not be possible in humans.
What did the research involve?
In the first part of the study, researchers used a previously identified protein, called thymosin β4, to reactivate a gene normally active only during embryo development. The activity of this gene would serve as a marker to indicate the activity of heart muscle progenitor cells, allowing the researchers to identify and confirm their presence throughout the study. They injected mice with thymosin β4, then took samples of heart tissue to study in the laboratory. They looked at the cells in this tissue to determine whether it looked like the heart tissue was making new heart muscle cells.
Next, the researchers looked at the effects of “priming” mice with thymosin β4 before they were induced to have a heart attack, to see whether the mice would make new heart cells after existing ones were damaged. They compared the mice primed with the thymosin β4 protein against mice injected with a placebo before having the induced heart attack. They also boosted the effects of the thymosin β4 by giving the mice another injection after their heart attacks. They then traced the development and movement of progenitor cells in the adult mouse hearts using the previously identified marker.
To determine the impact of protein priming on heart function and repair, researchers conducted a series of magnetic resonance imaging (MRI) scans at 7, 14 and 28 days after the heart attack.
What were the basic results?
The study found that the thymosin β4 protein reactivated dormant progenitor cells in the laboratory, which could develop into cells that had the characteristics of heart muscle cells.
They then looked at how progenitor cell development and migration were affected by priming live mice with thymosin β4 before an induced heart attack. When they compared priming the mice with thymosin β4 and injecting a placebo, they found that:
- Without protein priming, the marker gene for progenitor cells became active seven days after a heart attack.
- After thymosin β4 protein priming, the marker gene for progenitor cells became active earlier, two days after a heart attack.
- Compared to using a placebo, thymosin β4 protein priming resulted in significantly more activated progenitor cells throughout the heart seven days after a heart attack.
- Activated progenitor cells migrated to the site of injury and some of them developed into cells that had the characteristics of mature heart muscle cells.
- The new heart muscle tissue contracted along with existing heart muscle tissue 14 days after a heart attack, indicating its functional integration into the heart.
MRIs demonstrated that thymosin β4 priming in the mice resulted in:
- improved heart function after the heart attack, including improvements in the fraction of blood pumped with each heartbeat
- reductions in the volume of scar tissue and dead heart muscle cells
How did the researchers interpret the results?
Researchers concluded that priming adult mice with the thymosin β4 protein induced their hearts to respond to injury by producing new heart muscle cells. They say their results support the theory that the dormant progenitor cells exist in the outer layer of the adult heart.
The researchers recommend further research to identify more compounds to support the development of progenitor cell into heart muscle cells, as only a small proportion of them developed into new heart muscle cells in this study.
Conclusion
This animal study has demonstrated that thymosin β4 protein can induce the production of new heart muscle cells to repair heart tissue damaged by heart attack in mice. As this approach stimulated the heart’s own cells, it avoided the risk of rejection that would occur if tissues or cells had been grafted into the heart from another animal.
The thymosin β4 protein used to prime gene activity in the study has been previously shown to improve heart muscle cell survival soon after a heart attack. Researchers have added to the understanding of this protein’s role in protecting the heart from injury, and concluded that it is also involved in both initiating the development of dormant progenitor cells into mature heart cells and in movement of these cells to the site of injury.
Although reports of this research suggest that a fully developed heart repair pill already exists, this research is at a very early stage. Before human studies can be carried out, this experimental assessment of using thymosin β4 needs to be followed by further studies of the effectiveness and safety of such treatment in animals.
Crucially, the timing of a heart attack or similar injury in humans cannot be predicted. Therefore, it is not likely that doctors would be able to carry out priming in people a few days before a heart attack, as was the case in the mice in this study. Assuming that the protein is shown to have an effect in humans, it would be important to know whether administering thymosin β4 months or years before a heart attack, or immediately after a heart attack, could produce the same effect. As such, a “pill” that could regenerate human hearts is not yet a reality.
