Scientists from the United Kingdom have, for the first time, highlighted the natural regenerative abilities of a group of stem cells that live in our hearts. This particular study shows that these cells are responsible for repairing and regenerating muscle tissue that has been damaged by a heart attack. Such damage to the heart can lead to heart failure.
There is a robust debate as to the regenerative capacity of cardiac stem cells (CSCs) in the hearts a adult human beings. While many scientists are convinced that CSCs in the hearts of newborns have good regenerative ability, many remain unconvinced that adult CSCs can do similar things (see Zaruba, M.M., et al., Circulation 121, 1992–2000 and Jesty, S.A., et al., Proc. Natl. Acad. Sci. USA 109, 13380–13385). Nevertheless, an earlier paper showed that when introduced into heart muscle after a heart attack, CSCs will regenerate the lost heart muscle and blood vessels lost in the infarct (see Beltrami, A.P., et al., Cell 114, 763–776). Resolving this disagreement requires a different type of experiment.
In this paper, Bernardo Nadal-Ginard and colleagues from the and his collaborators at the Stem Cell and Regenerative Biology Unit at the Liverpool John Moores University in Liverpool and his collaborators from Italy used a different way to affect the heart. When heart attacks are experimentally induced in the heart of rodents, the infarcts are large and they kill off large numbers of CSCs. Therefore, Nadal-Ginard and others induced severe diffuse damage of the heart muscle that also spared the CSCs. They gave the mice a large dose of a drug called isoproterenol, which acts as a “sympathomimetic.” This is confusing science talk that simply means that the drug speeds the heart rate to the point where the heart muscle exhausts itself and then starts to die off. This treatment, however, spares the CSCs (see Ellison, G.M., et al., J. Biol. Chem. 282, 11397–11409).
When the heart muscle was damaged, the CSCs differentiated into heart muscle cells and other heart-specific cells and repaired the damage in the heart. Also, the repairing cells were in the heart and were not the result of bone marrow stem cells that migrated to the bone marrow, thus putting to rest a controversy that has lasted for some years that CSCs are the result of bone marrow stem cells that migrate to the heart.
Elimination of CSCs prevents heart repair after heart damage. If, however, these heart-based stem cells are replaced after damage, the heart repairs itself and the heart recovers its function, anatomical integrity, and cellular structure.
In other experiments, removal of cardiac stem cells (CSCs) and re-injection after a heart attack shows that the CSCs can home in and repair the damaged heart.
Since Nadal-Ginard showed that CSCs have a capacity to home to the damaged heart, less invasive treatments might be possible and that these treatments might even prevent heart failure after a heart attack in the future.
In a healthy heart, the quantity of CSCs is sufficient to repair heart muscle tissue. However, once the heart is damaged many of the CSCs are also damaged and cannot multiply or produce new muscle tissue. In these cases it could be possible to replace damaged CSCs with new ones that have been grown in the laboratory and administered intravenously.,
These new approaches involved maintaining or increasing the activity of CSCs in order to renew heart muscle and replace old, damaged cells. This new strategy will only require intravenous administration of CSCs and not require open heart procedures that require such a long time to recover.
These findings are very promising. The nest step is a clinical trial, which is due to start early 2014 and is aimed at assessing the safety and effectiveness of CSCs for preventing and treating heart failure in humans.