The Method of Establishing a Xenograft Animal Model

Abstract

Objective: 1) Establish a xenograft animal model of arteriovenous malformation (AVM), an uncommon and often incurable vascular anomaly. 2) Observe the morphological alterations and histological characteristics of xenograft AVM. Method: AVM specimens harvested from 4 patients were sectioned (5x5x5mm) and implanted in the subcutaneous dorsum of 5-Athymic Nude-Foxn1nu mice. 4 implants per animal were placed (N = 20). Specimens were harvested monthly and stained for hematoxylin and eosin (H&E). Immunohistochemistry for anti-human nuclear antigen and Ki-67 was performed. Histologic observations were recorded by 2-blinded pathologists. Results: Clinical characteristics and pathologic diagnosis of AVM was confirmed in each donor patient. A total of 85% (n = 17) of AVM xenografts survived the xenograft implantation. Survival was unrelated to date of harvest. The majority of implants slightly decreased in size by date of harvest (1-2mm). Pathologic diagnosis of a vascular anomaly was confirmed in each implant and demonstrated numerous small and medium-size vessels. A total of 76.5% (n = 13) of implants of surviving xenografts were positive for Ki-67 and anti-human nuclear antigen, confirming survival of the human derived tissue. Conclusion: We herein describe an animal model for AVM that may provide the first step for examining the pathophysiology and potential treatment of these difficult to treat lesions in vivo.