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Fixing broken hearts
BALTIMORE, Md.—Two stem cell studies at the University of Maryland School of Medicine show promise for cardiac patients. Both of the published studies were conducted on animal models, and the researchers anticipate that the next steps will be taken in human subjects.
One study, reported in the September issue of Stem Cells Translational Medicine, demonstrates how stem cells may significantly reduce the ripple-effect damage caused by a heart attack by evaluating the effects of expanding the stem cell treatment beyond the heart attack site. Because a heart attack has a ripple effect, much like an earthquake, the healthy tissue surrounding the damaged section gets overworked, leading to cardiac failure after the initial problem.
The researchers wanted to determine whether "mesenchymal stem cells improve the remodeling of the myocardium directly abutting the attack site," and whether they could "prevent changes to the heart's size, shape, structure and physiology resulting from the injury to its muscular tissue," according to Dr. Zhongium Wu, associate professor of surgery at the University of Maryland School of Medicine and a principal investigator in the study. The group has been conducting research on the structural change, functional alteration and molecular event of myocardial tissue of the heart during remodeling after myocardial infarction "in the clinically relevant ovine animal model," Wu explains.
The alteration of molecular proteins after myocardial infarction is time- and region-dependent, according to Wu.
"Mechanical stress is the major determinant of calcium cycling," so the researchers used ventricular assist devices to "unload the infarcted heart and reduce the mechanical stress/load on the myocardial tissue," he says, noting that the procedure normalized functional protein alteration, conserved electrophysiological calcium cycling and precluded damage of the calcium handling-related structures.
Then the researchers determined that the transplantation of mesenchymal stem cells into the infarcted myocardial tissue kept the adjacent tissue chemically and functionally intact. They believe that the sheep's heart size, blood volume, consistent coronary anatomy and lack of collateral coronary circulation are similar to a human with the same body weight, thus enhancing the prospect of human trials.
In the other study, researchers hypothesized that isolated neonatal-derived cardiac stem cells (CSCs) may have a higher regenerative ability than adult-derived CSCs and might better address the structural deficiencies of congenital heart disease in very young patients.
"Whereas adults with cardiac failure often have ischemic cardiomyopathy, pediatric cardiac heart failure is more varied and includes a spectrum of cardiomyopathies, congenital cardiac diseases and arrhythmias," according to a paper published in the September issue of Circulation, making it important to take a different view of the specific needs of young heart patients.
"We started five years ago, looking at stem cells for general heart patients, then getting more specific and asking fundamental questions: Are children's stem cells different? Are they functional in a regenerative model? How do they actually regenerate heart tissue?" explains Dr. Sunjay Kaushal, the senior member of the research team, associate professor of surgery at the University of Maryland School of Medicine and director of pediatric cardiac surgery at the University of Maryland Medical Center. They began a "head to-head-comparison" between the functionality of neonatal- derived and adult-derived stem cells and found that the former were three times as effective when used on children's hearts.
CSCs were taken from human babies undergoing cardiac surgical repair. They were isolated and tested in an established animal model of heart regeneration to determine heart function, scar formation and tissue regeneration.
The next steps are to test stem cells in "a controlled population of children with heart failure, hopefully within the next six to seven months," Kaushal says.
He envisions cellular therapy as either a standalone therapy for children with heart failure or an adjunct to medical and surgical treatments. While surgery can provide structural relief for some patients with congenital heart disease and medicine can boost heart function up to 2 percent, Kaushal believes that cellular therapy may improve heart function even more dramatically, possibly by 10, 12 or 15 percent—"a quantum leap in heart function improvement."
He concludes, "We are extremely excited and hopeful that this new cell- based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don't have other options."