Fixing broken hearts
University of Maryland cardiac studies explore use of stem cells to reduce ripple effect, help children
BALTIMORE, Md.—Two stem cell studiesat the University of Maryland School of Medicine show promise forcardiac patients. Both of the published studies were conducted onanimal models, and the researchers anticipate that the next stepswill be taken in human subjects.
One study, reported in the Septemberissue of Stem Cells Translational Medicine, demonstrates howstem cells may significantly reduce the ripple-effect damage causedby a heart attack by evaluating the effects of expanding the stemcell treatment beyond the heart attack site. Because a heart attackhas a ripple effect, much like an earthquake, the healthy tissuesurrounding the damaged section gets overworked, leading to cardiacfailure after the initial problem.
The researchers wanted to determinewhether "mesenchymal stem cells improve the remodeling of themyocardium directly abutting the attack site," and whether theycould "prevent changes to the heart's size, shape, structure andphysiology resulting from the injury to its muscular tissue,"according to Dr. Zhongium Wu, associate professor of surgery at theUniversity of Maryland School of Medicine and a principalinvestigator in the study. The group has been conducting research onthe structural change, functional alteration and molecular event ofmyocardial tissue of the heart during remodeling after myocardialinfarction "in the clinically relevant ovine animal model," Wuexplains.
The alteration of molecular proteinsafter myocardial infarction is time- and region-dependent, accordingto Wu.
"Mechanical stress is the majordeterminant of calcium cycling," so the researchers usedventricular assist devices to "unload the infarcted heart andreduce the mechanical stress/load on the myocardial tissue," hesays, noting that the procedure normalized functional proteinalteration, conserved electrophysiological calcium cycling andprecluded damage of the calcium handling-related structures.
Then the researchers determined thatthe transplantation of mesenchymal stem cells into the infarctedmyocardial tissue kept the adjacent tissue chemically andfunctionally intact. They believe that the sheep's heart size,blood volume, consistent coronary anatomy and lack of collateralcoronary circulation are similar to a human with the same bodyweight, thus enhancing the prospect of human trials.
In the other study, researchershypothesized that isolated neonatal-derived cardiac stem cells (CSCs)may have a higher regenerative ability than adult-derived CSCs andmight better address the structural deficiencies of congenital heartdisease in very young patients.
"Whereas adults with cardiac failureoften have ischemic cardiomyopathy, pediatric cardiac heart failureis more varied and includes a spectrum of cardiomyopathies,congenital cardiac diseases and arrhythmias," according to a paperpublished in the September issue of Circulation, making itimportant to take a different view of the specific needs of youngheart patients.
"We started five years ago, lookingat stem cells for general heart patients, then getting more specificand asking fundamental questions: Are children's stem cellsdifferent? Are they functional in a regenerative model? How do theyactually regenerate heart tissue?" explains Dr. Sunjay Kaushal, thesenior member of the research team, associate professor of surgery atthe University of Maryland School of Medicine and director ofpediatric cardiac surgery at the University of Maryland MedicalCenter. They began a "head to-head-comparison" between thefunctionality of neonatal-derived and adult-derived stem cells andfound that the former were three times as effective when used onchildren's hearts.
CSCs were taken from human babiesundergoing cardiac surgical repair. They were isolated and tested inan established animal model of heart regeneration to determine heartfunction, scar formation and tissue regeneration.
The next steps are to test stem cellsin "a controlled population of children with heart failure,hopefully within the next six to seven months," Kaushal says.
He envisions cellular therapy as eithera standalone therapy for children with heart failure or an adjunct tomedical and surgical treatments. While surgery can provide structuralrelief for some patients with congenital heart disease and medicinecan boost heart function up to 2 percent, Kaushal believes thatcellular therapy may improve heart function even more dramatically,possibly by 10, 12 or 15 percent—"a quantum leap in heartfunction improvement."
He concludes, "We are extremelyexcited and hopeful that this new cell-based therapy can play animportant role in the treatment of children with congenital heartdisease, many of whom don't have other options."