May 1, 2014
Heart Muscles Repaired After Heart Attack Using Human Embryonic Stem Cells
April Flowers for redOrbit.com - Your Universe Online
When a heart attack occurs, the oxygen-rich blood that normally flows through is interrupted by the blockage in an artery. The longer that blood flow is restricted or cut off, the more tissue and muscle in the area dies or is scarred. The eventual result can be heart failure, especially if one heart attack is followed by another.
A new study from the University of Washington, however, reveals improvement in those results. The findings, published online in Nature, demonstrate that damaged heart muscles in monkeys have been restored by the use of heart cells created from human embryonic stem cells. The exciting implication, according to the research team, is that their approach should also be feasible in humans.
"Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to remuscularize damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart," said Dr. Charles Murry, UW professor of pathology and bioengineering and director of the UW Center for Cardiovascular Biology, in a recent statement.
Murray, who collaborated with Dr. Michael Laflamme and other colleagues at the UW Institute for Stem Cell & Regenerative Medicine, predicts clinical trials with humans within the next four years.
[ Watch the Video: Regenerating Heart Muscle Damage With Stem Cell Therapy ]
For the study, the researchers induced controlled myocardial infarctions, a type of heart attack, in anesthetized pigtail macaques, by blocking the coronary artery for 90 minutes. This is the accepted practice for studying myocardial infarction in primates.
Coronary artery disease is the primary culprit in myocardial infarctions in humans. The infarcted heart muscle, damaged by a lack of oxygen, does not grow back, leaving the heart less able to pump blood. This often leads to heart failure, the leading cause of cardiovascular death. Researchers hope to use new heart cells created from stem cells in order to restore normal function to the failing heart.
One billion heart muscle cells derived from human embryonic stem cells, called human embryonic stem cell-derived cardiomyocytes, were injected into the infarcted muscle of the macaques two weeks after the induced myocardial infarctions. As with any transplantation, the monkeys had been put on immunosuppressive therapy to prevent their bodies from rejecting the heart cells.
The damaged heart tissue was infiltrated by the stem cell derived heart muscle cells over the following weeks. These cells then matured, assembled into muscle fibers and began to beat in synchrony with the macaques' own heart cells. The stem cell derived cells appeared to be fully integrated into the heart by the end of three months.
Dr. Laflamme noted that, on average, the transplanted cells regenerated 40 percent of the damaged heart tissue.
"The results show we can now produce the number of cells needed for human therapy and get formation of new heart muscle on a scale that is relevant to improving the function of the human heart," Laflamme told Michael McCarthy of UW's HSNewsBeat.
The research team used ultrasound images of the monkeys' hearts. These images showed that some, but not all, of the monkeys had an improvement in the ejection fraction, an indication of the hearts ability to pump blood. The images also revealed that the arteries and veins from the macaques' original heart tissue grew into the new tissue. This is the first time researchers have been able to show that a host animal's blood vessels will grow into and nurture a large stem cell derived graft like this.
Of course, there are side effects to such a procedure, the most troubling of which were episodes of irregular heartbeats, known as arrhythmias. The macaques suffered arrhythmias in the weeks after the stem cell injections, according to Murray. During these episodes, however, none of the macaques suffered any symptoms, and the arrhythmias disappeared after two to three weeks as the cells matured and gained electric stability.
This study was funded by several National Institutes of Health (NIH) grants and an Institute of Translational Health Sciences/Washington National Primate Research Center Ignition Award.
The research team intends to continue their studies, hoping to reduce the risk of arrhythmias, perhaps with the use of more electrically mature cells. Another goal is to provide definitive proof that the stem cells are strengthening the heart's pumping power.
"These cells have improved the mechanical function in every other species in which they have been tested, so we are optimistic they will do so in this model as well," Murry concluded.