Cells carry the genome in their nucleus, and the genes that are expressed give a cell its identity. Researchers have been able to manipulate gene expression to alter the identity of cells in various ways. For example, adult skin cells can be reprogrammed into pluripotent stem cells, which have the ability to become any type of cell in the body. For that reason, stem cells have long held promise in regenerative medicine, such as in the repair of heart tissue that gets damaged or dies during a heart attack.
Scientists have now developed a method for reprogramming heart muscle cells to heal heart attack damage. The work, which was tested successfully in a mouse model, has been reported in Science Translational Medicine.
Heart attacks occur because something obstructs the flow of blood to the heart, starving cells of oxygen and preventing the muscle from functioning; it may happen because of a blood clot or plaque in the coronary artery; the blood flow might be partially or totally blocked. Sudden cardiac arrest may also occur when the heart stops pumping blood because of an electrical problem in the heart, called an arrhythmia. Heart cells die off during a heart attack, and while that may not be fatal, it can cause permanent scarring.
In this research, the scientists were able to prevent the scarring that can accompany a heart attack in an animal model.
Heart cells or cardiomyocytes are not able to regenerate on their own. So when cardiomyocytes are damaged beyond repair during a heart attack, they stay damaged. This work found a way to stimulate regeneration in heart cells with the combination of genes that create stem cells from reprogrammed adult cells, the Yamanaka factors. The genes that enable these cells to renew are c-Myc, Klf4, Sox2, and Oct4. In this study, the reprogramming was under the control of an antibiotic called doxycycline.
A mouse model that carried the reprogrammed cells was given doxycycline just before and after heart damage occurred. In both cases, heart cells regenerated and the function of the heart got better. When doxycycline was only given to the mice six days after their hearts were damaged, there was no regeneration. The researchers concluded that there is only so much time to use this approach to heal the heart before it's not possible (with this approach, or right now, any others). There was also a limit to the beneficial effect; if doxycycline was given to the mice for too long, they began to develop cancerous tumors.
More work will be needed before researchers know if this approach could work in humans, but it shows that after years of research, scientists have been able to find a way to regenerate damaged heart cells.
Sources: Medical Xpress, Science Translational Medicine
