Corticosteroid Suppression in Infant Hemangioma-Derived Stem Cells

Infantile hemangioma is the most common tumor of infancy. Although most can be observed for spontaneous involution, approximately 10% require intervention because of ulceration, disfigurement, or obstructed vision, airway, or other vital function. Corticosteroids (systemic or intralesional) have been the standard therapy for problematic hemangiomas since the 1960s, but how they stabilize proliferation and accelerate regression is not known.

When injected into nude mice, hemangioma-derived stem cells (HDSCs) demonstrate unique vasculogenic activity — the de novo formation of blood vessels. In contrast, hemangioma-derived endothelial cells and hemangioma-derived endothelial progenitor cells display angiogenic rather than vasculogenic activity in mice. To investigate the effect of corticosteroid treatment on vasculogenesis in infantile hemangioma, researchers treated HDSCs with dexamethasone in vitro and in vivo in nude mice.

Systemic dexamethasone treatment led to dose-dependent inhibition of tumor vasculogenesis. Pretreatment of the HDSCs in vitro before implantation also inhibited vasculogenesis. In vitro, dexamethasone suppressed production of vascular endothelial growth factor A (VEGF-A) by HDSCs but not by hemangioma-derived endothelial cells or by human umbilical-vein endothelial cells. In vivo, silencing VEGF-A in HDSCs reduced vasculogenesis. VEGF-A was detected in the proliferating phase but not in the involuting phase of the hemangioma.

The authors believe that apoptosis is an unlikely mechanism of action of corticosteroid therapy, as dexamethasone-induced apoptosis of HDSCs and hemangioma-derived endothelial progenitor cells occurred only at doses 1000 times that required to produce antivasculogenic activity.