title: A xenograft animal model of human arteriovenous malformations.
abstract: BACKGROUND
  Arteriovenous malformations (AVMs) are a type of high-flow vascular malformations that most commonly occurs in the head and neck. They are present at birth but are usually clinically asymptomatic until later in life. The pathogenesis of AVMs remains unclear and therapeutic approaches to AVMs are unsatisfied. In order to provide a tool for studying the pathogenesis and therapies of this disease, we established and studied a xenograft animal model of human AVMs.
  
  
  METHODS
  Fresh human AVMs specimens harvested from 4 patients were sectioned (5 x 5 x 5 mm) and xenografted subcutaneously in 5 immunologically naïve nude mice (Athymic Nude-Foxn1(nu)). Each mouse had four pieces specimens in four quadrants along the back. The grafts were observed weekly for volume, color and texture. The grafts were harvested at every 30 days intervals for histologic examination. All grafts (n = 20) were sectioned and stained for hematoxylin and eosin (H&E). Comparative pathologic evaluation of the grafts and native AVMs were performed by two blinded pathologists. Immunohistochemical examination of human-specific nuclear antigen, vascular endothelial growth factor receptor-2 (VEGFR-2) and Ki-67 was performed.
  
  
  RESULTS
  Clinical characteristics and pathologic diagnosis of native human derived AVMs were confirmed. 85% (n = 17) of AVM xenografts survived although the sizes decreased after implantation. Histological examination demonstrated numerous small and medium-size vessels and revealed structural characteristics matching the native AVMs tissue.76.5% (n = 13) of the surviving xenografts were positive for Ki-67 and human-specific nuclear antigen suggesting survival of the human derived tissue, 52.9% (n = 9) were positive for VEGFR-2.
  
  
  CONCLUSIONS
  This preliminary xenograft animal model suggests that AVMs can survive in the nude mouse. The presence of human-specific nuclear antigen, VEGFR-2, and Ki-67 demonstrates the stability of native tissue qualities within the xenografts.
authors.forename: Fang
authors.initials: F
authors.lastname: Hou
authors.forename: Yuemeng
authors.initials: Y
authors.lastname: Dai
authors.forename: James Y
authors.initials: JY
authors.lastname: Suen
authors.forename: Chunyang
authors.initials: C
authors.lastname: Fan
authors.forename: Ali G
authors.initials: AG
authors.lastname: Saad
authors.affiliation: Center for the Investigation of Congenital Aberrancies of Vascular Development, Little Rock, AR, USA. gtrichter@uams.edu.
authors.forename: Gresham T
authors.initials: GT
authors.lastname: Richter
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001165:Arteriovenous Malformations / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D040301:Vascular Endothelial Growth Factor Receptor-2