A novel three-dimensional model of Infantile Haemangioma.

Abstract

Infantile Haemangioma (IH) is vascular tumour in infants exhibiting rapid proliferation and angiogenesis followed by gradual involution.10% of cases are associated with disfiguring complications and requires medical interventions with β-blockers such as propranolol, surgery, or laser therapy. An in vitro IH three-dimensional (3D) model will improve our understanding of the disease mechanism(s). We have isolated and expanded CD31+ endothelial cells (HemEC) from patient-derived IH cell lines, and then grown as spheroids in StemDIFF Endothelial expansion media. These were then embedded in extracellular matrix hydrogel with reduced growth factors to initiate angiogenic sprouting. HemEC spheroids expressed CD31, GLUT1, VEGFR2, CD44, Vimentin, CD133 but not SMA, 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 this 3D angiogenesis model was tested using propranolol to inhibit sprouting of spheroids with increased toxicity response. This study reports the development of a 3D model of IH that recapitulates angiogenic features of IH for molecular analysis and drug screening.