Background: Arteriovenous malformations (AVMs) are a type of high-flow vascular malformations that most\r\ncommonly occurs in the head and neck. They are present at birth but are usually clinically asymptomatic until later\r\nin life. The pathogenesis of AVMs remains unclear and therapeutic approaches to AVMs are unsatisfied. In order to\r\nprovide a tool for studying the pathogenesis and therapies of this disease, we established and studied a xenograft\r\nanimal model of human AVMs.\r\nMethods: Fresh human AVMs specimens harvested from 4 patients were sectioned (5x5x5 mm) and xenografted\r\nsubcutaneously in 5 immunologically na�¯ve nude mice (Athymic Nude-Foxn1nu). Each mouse had four pieces\r\nspecimens in four quadrants along the back. The grafts were observed weekly for volume, color and texture. The\r\ngrafts were harvested at every 30 days intervals for histologic examination. All grafts (n = 20) were sectioned and\r\nstained for hematoxylin and eosin (H&E). Comparative pathologic evaluation of the grafts and native AVMs were\r\nperformed by two blinded pathologists. Immunohistochemical examination of human-specific nuclear antigen,\r\nvascular endothelial growth factor receptor-2 (VEGFR-2) and Ki-67 was performed.\r\nResults: Clinical characteristics and pathologic diagnosis of native human derived AVMs were confirmed. 85%\r\n(n = 17) of AVM xenografts survived although the sizes decreased after implantation. Histological examination\r\ndemonstrated numerous small and medium-size vessels and revealed structural characteristics matching the native\r\nAVMs tissue.76.5% (n = 13) of the surviving xenografts were positive for Ki-67 and human-specific nuclear antigen\r\nsuggesting survival of the human derived tissue, 52.9% (n = 9) were positive for VEGFR-2.\r\nConclusions: This preliminary xenograft animal model suggests that AVMs can survive in the nude mouse. The\r\npresence of human-specific nuclear antigen, VEGFR-2, and Ki-67 demonstrates the stability of native tissue qualities\r\nwithin the xenografts.
Loading....