Tan S T, Hasan Q, Velickovic M, Rüger B M, Davis R P, Davis P F
Swee Tan Plastic Surgery Trust, Bowen Hospital, Wellington, New Zealand.
Mod Pathol. 2000 Jan;13(1):92-9. doi: 10.1038/modpathol.3880014.
Hemangioma, the most common tumor of infancy, is characterized by a proliferation of capillary endothelial cells with multilamination of the basement membrane and accumulation of cellular elements, including mast cells. The initial rapid growth is followed by an inevitable but slow involution. The currently available therapies are empirical and unsatisfactory because what is known of the cellular and molecular basis of hemangioma development is rudimentary. Advances in the understanding of its programmed biologic behavior 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-salt, minimal medium. A complex network of microvessels grows out from the tissue fragments. Biopsies taken from all three phases of hemangioma development were cultured successfully; proliferative phase samples developed microvessels in 1 to 4 days, involuting phase in 5 to 7 days, and involuted phase in 7 to 12 days. The relative growth rates of the microvessels in the culture of biopsies taken from different stages of hemangioma development reflect the growth patterns seen clinically. This model has been validated using histochemistry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Comparison of the number, localization, and phenotype of endothelial and mast cells and the distribution of basement membrane constituents (type IV collagen, perlecan, and laminins) and growth factors (basic fibroblast growth factor, vascular endothelial growth factor, transforming growth factor-betas) 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 precise cellular, biochemical, and molecular basis of hemangioma It may also help to elucidate the mechanisms of action of existing therapies and may lead to the identification of novel treatments for hemangioma.
血管瘤是婴儿期最常见的肿瘤，其特征是毛细血管内皮细胞增殖，基底膜多层化，以及包括肥大细胞在内的细胞成分积聚。最初的快速生长之后是不可避免但缓慢的消退。目前可用的治疗方法是经验性的且不尽人意，因为对血管瘤发生的细胞和分子基础的了解还很初步。由于缺乏有效的人类模型，对其程序性生物学行为的理解进展受阻。我们在此报告一种新型的体外培养系统，它是一种有用的血管瘤人类模型。将一小片血管瘤活检组织嵌入培养板孔中的纤维蛋白凝胶中，并在无血清、缓冲盐、基本培养基中孵育。微血管的复杂网络从组织碎片中生长出来。取自血管瘤发展的所有三个阶段的活检组织均成功培养；增殖期样本在1至4天内形成微血管，消退期在5至7天，消退完成期在7至12天。取自血管瘤不同发展阶段活检组织培养物中微血管的相对生长速率反映了临床上观察到的生长模式。该模型已通过组织化学、免疫组织化学和逆转录聚合酶链反应进行了验证。比较活检组织和培养后组织中内皮细胞和肥大细胞的数量、定位和表型，以及基底膜成分（IV型胶原、巢蛋白和层粘连蛋白）和生长因子（碱性成纤维细胞生长因子、血管内皮生长因子、转化生长因子-β）的分布，结果表明原始组织的许多特征在培养中得以保留。这种血管瘤的体外人类模型克服了与早期模型相关的一些缺陷。它为研究血管瘤精确的细胞、生化和分子基础提供了机会。它还可能有助于阐明现有治疗方法的作用机制，并可能导致识别出治疗血管瘤的新方法。
