A xenograft animal model of human arteriovenous malformations

Fang Hou, Yuemeng Dai, James Y. Suen, Chunyang Fan, Ali Saad, Gresham T. Richter

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (5x5x5 mm) and xenografted subcutaneously in 5 immunologically naïve nude mice (Athymic Nude-Foxn1nu). 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.

Original languageEnglish (US)
Article number199
JournalOrphanet Journal of Rare Diseases
Volume8
Issue number1
DOIs
StatePublished - Dec 30 2013
Externally publishedYes

Fingerprint

Arteriovenous Malformations
Heterografts
Animal Models
Vascular Endothelial Growth Factor Receptor-2
Nuclear Antigens
Transplants
Nude Mice
Vascular Malformations
Hematoxylin
Eosine Yellowish-(YS)
Population Groups
Neck
Color
Head
Parturition
Survival

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

A xenograft animal model of human arteriovenous malformations. / Hou, Fang; Dai, Yuemeng; Suen, James Y.; Fan, Chunyang; Saad, Ali; Richter, Gresham T.

In: Orphanet Journal of Rare Diseases, Vol. 8, No. 1, 199, 30.12.2013.

Research output: Contribution to journalArticle

Hou, Fang ; Dai, Yuemeng ; Suen, James Y. ; Fan, Chunyang ; Saad, Ali ; Richter, Gresham T. / A xenograft animal model of human arteriovenous malformations. In: Orphanet Journal of Rare Diseases. 2013 ; Vol. 8, No. 1.
@article{1460b37fb55f48759c9de1a5d49ac335,
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 (5x5x5 mm) and xenografted subcutaneously in 5 immunologically na{\"i}ve nude mice (Athymic Nude-Foxn1nu). 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.",
author = "Fang Hou and Yuemeng Dai and Suen, {James Y.} and Chunyang Fan and Ali Saad and Richter, {Gresham T.}",
year = "2013",
month = "12",
day = "30",
doi = "10.1186/1750-1172-8-199",
language = "English (US)",
volume = "8",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A xenograft animal model of human arteriovenous malformations

AU - Hou, Fang

AU - Dai, Yuemeng

AU - Suen, James Y.

AU - Fan, Chunyang

AU - Saad, Ali

AU - Richter, Gresham T.

PY - 2013/12/30

Y1 - 2013/12/30

N2 - 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 (5x5x5 mm) and xenografted subcutaneously in 5 immunologically naïve nude mice (Athymic Nude-Foxn1nu). 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.

AB - 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 (5x5x5 mm) and xenografted subcutaneously in 5 immunologically naïve nude mice (Athymic Nude-Foxn1nu). 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.

UR - http://www.scopus.com/inward/record.url?scp=84891362378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891362378&partnerID=8YFLogxK

U2 - 10.1186/1750-1172-8-199

DO - 10.1186/1750-1172-8-199

M3 - Article

VL - 8

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 1

M1 - 199

ER -