Induction of autoimmune abdominal aortic aneurysm in pigs - A novel large animal model

Abstract

BackgroundAbdominal aortic aneurysm (AAA) is a common disease with a high mortality. Many animal models have been developed to further understand the pathogenesis of the disease, but no large animal model has been developed to investigate the autoimmune aspect of AAA formation. The aim of this study was to develop a large animal model for abdominal aortic aneurysm induction through autoimmunity by performing sheep-to-pig xenotransplantation.MethodsSix pigs underwent a xenotransplantation procedure where the infrarenal porcine aorta was replaced by a decellularized sheep aorta. In the following 47 days, the AP-diameter of the xenografts was measured using ultrasound once a week. All xenografts were harvested for histological analyses.ResultsAll the xenografts formed aneurysms with a mean increase in AP-diameter of 80.98 ± 30.20% (p < 0.005). The ultrasound measurements demonstrated a progressive aneurysmal expansion with no sign of halting towards the end of the follow-up period. Histology showed destruction of tunica media and the elastic tissue, neointimal hyperplasia, adventitial thickening with neovascularization, infiltration of lymphocytes and granulocytes, and in some cases intramural haemorrhaging.ConclusionWe developed a novel large animal AAA model by infrarenal aortic sheep-to-pig xenograph transplantation resulting in autoimmune AAA induction with continuously progressive aneurysmal growth. This model can be used to provide a better understand the autoimmune aspect of AAA formation in large animals.

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

“…Recently, a large animal xenograft study implanted decellularized sheep aorta into pigs. 24 There was an increase in aortic diameter of 81 ± 30% in the following 47 days. Owing to the extensive weight gain in these conventional pigs, longer follow-up was impossible.…”

Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models

“…The therapeutic efficacy of the IGF1C-loaded hydrogel was further evaluated in a xenograft model in pigs whose infrarenal aorta was replaced by a decellularized aorta from sheep ( 40 ). For the prevention study, the IGF1C-loaded hydrogel was injected at the time of xenograft implantation (Fig.…”

“…The aorta was rinsed with 0.9% sterile saline during this procedure. Decellularization was performed as previously described with minor modifications ( 40 ). The aortas were treated with 0.5% SDS in tris-EDTA buffer (TE buffer) at room temperature for 24 hours under gentle shaking.…”

A novel animal model of abdominal aortic aneurysm by mechanical injury

“…The xenograft model uses implanted xenograft arterial tissues to generate AAAs using the rejection of the implanted tissue by the immune response ( 7 , 19 ). Models which use knockout animals, which focus on the disruption of one or more gene alleles resulting in the creation of strain-deficient animals have also been previously reported ( 2 ).…”