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Study shows cardiac stem cells outperform bone marrow stem cells in treating heart attacks

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As both of these cell types are currently in clinical trials, these results are significant because they are the first direct comparison of their therapeutic capability in vivo, the researchers say.

“This research — showing that CSCs can be 30 times more potent than MSCs — is significant because it can impact the design of future clinical trials,” said Dr. Anthony Atala, director of the Wake Forest Institute of Regenerative Medicine and editor of STEM CELLS Translational Medicine. “The results from the study, one of a few to compare efficacy, have the potential to make the translation process more efficient, speeding the development of new effective therapies.”

The researchers conducted their study using mice models with induced acute myocardial infarction. The mice then received human fetal CSCs or either an equivalent (low dose) or ~30-fold greater number (high dose) of MSCs. Cells were injected immediately after the attack. A control group received PBS. The researchers performed additional experiments to address whether adult CSCs are as efficient as fetal CSCs. The fetal stem cells outperformed the adult-cultured CSCs, as expected; still, the researchers concluded that the latter were more potent than high-dose MSCs in treating a heart attack.

The animals were then evaluated at various intervals over a period of eight weeks. The results showed that the CSCs improved the left ventricle, which had been enlarged by the heart attack, plus lowered the ejection fraction. While the high doses of the MSCs showed similar results, the low-doses of MSCs had no effect.

“This study was motivated by the huge advances occurring in the translation of stem cell therapeutics for heart disease,” said Dr. Joshua Hare, senior author of the study and director of UM’s Interdisciplinary Stem Cell Institute. “While many candidate therapies are being considered there are few studies comparing relative efficacy. This study shows that tissue specific cardiac stem cells are highly potent, but that bone marrow stem cells are also efficacious. We hope these results will help guide future clinical trials of cell-based therapy for heart disease.”

In addition, said Dr. Behzad Oskouei of UM’s Interdisciplinary Stem Cell Institute, “All cell therapies studied improved myocardial contractility, but the CSCs preferentially reduced scar size and vascular afterload. Engraftment and trilineage [cardiomyocyte, vascular smooth muscle, endothelial cell] differentiation was also substantially greater with CSCs than with MSCs.”

“It is clear that CSCs are superior in this regard and have potential advantages over MSCs to promote repair following ischemic heart damage. Furthermore, they are effective at a surprisingly low-dose/efficacy ratio,” Dr. Oskouei noted. “These findings offer key new insights into the cellular characteristics underlying successful cell-based cardiac repair.”

 

The full article, “Increased Potency of Cardiac Stem Cells Compared with Bone Marrow Mesenchymal Stem Cells in Cardiac Repair,” can be accessed at: http://www.stemcellstm.com/content/early/2012/02/07/sctm.2011-0015.full.pdf.