A novel three-dimensional model of infantile haemangioma

Abstract

Background: Infantile haemangioma (IH) is vascular tumour in infants that exhibits rapid proliferation and angiogenesis followed by gradual involution. Ten per cent of cases are associated with disfiguring complications that require medical intervention with beta blockers, surgery or laser therapy. Objectives: To improve our understanding of the disease mechanisms of IH with an in vitro three-dimensional model. Methods: We isolated and expanded CD31+ endothelial cells (HemECs) from patient-derived IH cell lines and grew them as spheroids in STEMdiffTM Endothelial Expansion Medium. The cells were then embedded in an extracellular matrix hydrogel with reduced growth factors to initiate angiogenic sprouting. Results: HemEC spheroids expressed CD31, glucose transporter 1, vascular endothelial growth factor receptor 2, CD44, vimentin and CD133 but not smooth muscle actin, indicating their similarity to immature IH blood vessels and their angiogenic potential. Proteomic analysis revealed similar homology in terms of protein expression in spheroids and IH tissue. The high-throughput application of the three-dimensional angiogenesis model was tested using propranolol to inhibit sprouting of spheroids with increased toxicity response. Conclusions: This study reports the development of a three-dimensional model of IH that closely resembles the angiogenic features of IH for molecular analysis and drug screening.