The aim of this study was to develop a reproducible rat model of lymphatic malformation. Different types of adjuvant, with and without vascular endothelial growth factor (VEGF)-C, was injected into the neck and floor of the mouth of rats. The rats were killed 2 months after the injection. Injected rats developed cystic lesions in the neck and floor of the mouth. Immunohistochemical examination revealed that the cysts were lined by endothelium, which expressed the lymphatic endothelial markers LYVE-1 and VEGF receptor-3. Raman spectra of the liquid contents of the cysts were similar in all injected rats. Transmission electron microscopy revealed that the endothelial cells had no basement membrane or surrounding pericytes. The cystic lesions were consistent with human lymphatic malformation. This animal model could be used to investigate pathogenesis of lymphatic malformation and its responses to candidate therapies.
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