NEW YORK (Jan. 4, 2013) -- A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.
"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."
"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."
This research could be speeded up if people with heart failure were allowed to volunteer for high risk gene therapy experiments. People with heart failure are already getting ready to check out from the life hotel. They should be allowed to take a big risk for themselves and biomedical science.
Even with the slow rate at which animal experiment results get turned into human therapies I'd be quite surprised if we did not have gene therapies for repair of damaged hearts in 15 years.
During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.
Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.)
The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)
The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.
We might also benefit from enhancing the ability for a heart to repair itself before a heart begins to fail. Humans turn out to make cardiomyocyte heart cells up to age 20. If we could use gene therapy or cell therapy to reactivate that capability in our 50s or 60s we might be able to turn back the clock on heart aging.
Boston, Mass. — Researchers at Boston Children's Hospital have found, for the first time that young humans (infants, children and adolescents) are capable of generating new heart muscle cells. These findings refute the long-held belief that the human heart grows after birth exclusively by enlargement of existing cells, and raise the possibility that scientists could stimulate production of new cells to repair injured hearts.
Findings of the study, "Cardiomyocyte proliferation contributes to post-natal heart growth in young humans," were published in Proceedings of the National Academy of Sciences, Online Early Edition, the week of Jan 7-Jan 11, 2013. The study was led by Bernhard Kühn, MD, of the Department of Cardiology at Boston Children's.
Beginning in 2009, Dr. Kühn and his team looked at specimens from healthy human hearts, ranging in age from 0 to 59 years. Using several laboratory assays, they documented that cells in these hearts were still dividing after birth, significantly expanding the heart cell population. The cells regenerated at their highest rates during infancy. Regeneration declined after infancy, rose during the adolescent growth spurt, and continued up until around age 20.
|Share |||Randall Parker, 2013 January 10 08:56 PM|