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Hemangioma stem cells, pretreated with steroids, formed no blood vessels when suspended in a gel and injected into mice (left). When endothelial cell progenitors were treated the same way, blood vessels still formed (right). |
Since the 1960s, problematic hemangiomas have been treated with corticosteroids. But steroids' mechanism of action has been unknown, side effects are considerable, and 15 to 30 percent of hemangiomas don't respond. Researchers led by Joyce Bischoff, PhD, in Children's Vascular Biology Program, recently discovered that hemangiomas originate from stem cells. They now show that steroids interfere with these cells and how they work, information that may help their lab find a better approach to treating hemangioma.
Hemangiomas consist of tangled masses of blood vessels, and since endothelial cells are the major cell type in vessels, they were assumed to be steroids' target. But in the March 18 New England Journal of Medicine, Shoshana Greenberger, MD, PhD, in Bischoff's lab demonstrates that steroids act on the much rarer hemangioma stem cells, blocking their ability to stimulate blood vessel growth by shutting down production of vascular endothelial growth factor (VEGF-A), a well-known stimulator of angiogenesis. "We already have drugs targeting VEGF, so our findings open the way to finding a more specific, safer therapy for hemangioma," says Dr. Greenberger.
Dr. Bischoff's lab is now searching for other agents that would shut down cellular VEGF-A, stop the proliferation of hemangioma stem cells and prevent them from forming unwanted blood vessels.
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