Pericytes From Infantile Hemangioma Display Proangiogenic Properties and Dysregulated Angiopoietin-1

Abstract

Infantile hemangioma (IH) is a rapidly growing vascular tumor affecting newborns. It is composed of immature endothelial cells and pericytes that proliferate into a disorganized mass of blood vessels. We isolated pericytes from IH (Hem-pericytes) to test our hypothesis that Hem-pericytes are unable to stabilize blood vessels. We injected pericytes in vivo, in combination with endothelial cells, and found that Hem-pericytes formed more microvessels compared with control retinal pericytes. We, thereby, analyzed proangiogenic properties of the Hem-pericytes. They grew fast in vitro, and were unable to stabilize endothelial cell growth and migration, and expressed high levels of vascular endothelial growth factor-A compared with retinal pericytes. Hem-pericytes from proliferating phase IH showed lower contractility in vitro, compared with Hem-pericytes from the involuting phase and retinal pericytes. Consistent with a diminished ability to stabilize endothelium, angiopoietin 1 was reduced in Hem-pericytes compared with retinal pericytes. Normal retinal pericytes in which angiopoietin 1 was silenced produced conditioned medium that stimulated endothelial cell proliferation and migration. We report the first successful isolation of patient-derived pericytes from IH tissue. Hem-pericytes exhibited proangiogenic properties and low levels of angiopoietin 1, consistent with a diminished ability to stabilize blood vessels in IH.