A novel in vitro human model of hemangioma

Hemangioma, the most common tumor of infancy, is characterized by a prolife ration of capillary endothelial cells with multilamination of the basement membrane and accumulation of cellular elements, including mast cells. The i nitial rapid growth is followed by an inevitable but slow involution. The c urrently available therapies are empirical and unsatisfactory because what is known of the cellular and molecular basis of hemangioma development is r udimentary. Advances in the understanding of its programmed biologic behavi or has been hampered by the lack of a valid human model. We report here a novel in vitro culture system that is a useful human model of hemangioma. A small fragment of hemangioma biopsy is embedded in fibrin gel in a well of culture plates and incubated in a serum-free, buffered-sa lt, minimal medium. A complex network of microvessels grows out from the ti ssue fragments. Biopsies taken from all three phases of hemangioma developm ent were cultured successfully; proliferative phase samples developed micro vessels in 1 to 4 days, involuting phase in 5 to 7 days, and involuted phas e in 7 to 12 days. The relative growth rates of the microvessels in the cul ture of biopsies taken from different stages of hemangioma development refl ect the growth patterns seen clinically. This model has been validated using histochemistry, immunohistochemistry, a nd reverse transcriptase-polymerase chain reaction. Comparison of the numbe r, localization, and phenotype of endothelial and mast cells and the distri bution of basement membrane constituents (type IV collagen, perlecan, and l aminins) and growth factors (basic fibroblast growth factor, vascular endot helial growth factor, transforming growth factor-ps) in the biopsy and the tissue after culture shows that many of the characteristics of the original tissues were retained in culture. This in vitro human model of hemangioma overcomes some of the deficiencies associated with earlier models. It offers an opportunity for studying the p recise cellular, biochemical, and molecular basis of hemangioma It may also help to elucidate the mechanisms of action of existing therapies and may l ead to the identification of novel treatments for hemangioma.