Combined abdominal heterotopic heart and aorta transplant model in mice

Abstract

Background Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV. Methods The middle of the infrarenal aorta of the recipient mouse was ligatured between the renal artery and its bifurcation. Proximal and distal aortotomies were performed at this site above and below the ligature, respectively, for the subsequent anastomoses of the donor aorta and heart grafts to the recipient infrarenal aorta in an end-to-side fashion. The distal anastomotic site of the recipient infrarenal aorta was connected with the outlet of the donor aorta. Uniquely, the proximal anastomotic site on the recipient infrarenal aorta was shared to connect with both the inlet of the donor aorta and the inflow tract to the donor heart. The outflow tract from the donor heart was connected to the recipient inferior vena cava (IVC). Results The median times for harvesting the heart graft, aorta graft, recipient preparation and anastomosis were 11.5, 8.0, 9.0 and 40.5 min, respectively, resulting in a total median ischemic time of 70 min. The surgery survival rate was more than 96% (29/30). Both the syngeneic C57Bl/6 aorta and heart grafts survived more than 90 days in 29 C57Bl/6 recipients. Further, Balb/c to C57Bl/6 allografts treated with anti-CD40L and CTLA4.Ig survived more than 90 days with a 100% (3/3) survival rate. (3/3). Conclusions This model is presented as a new tool for researchers to investigate transplant immunology and assess immunosuppressive strategies. It is possible to share a common anastomotic

MFG-E8 Reduces Aortic Intimal Proliferation in a Murine Model of Transplant Vasculopathy

“…Our study encounters several limitations. First, though widely used, the accuracy of aorta transplantation in modelling TV and chronic rejection is debated [35][36][37], mostly because of the endothelial nature of the graft. Second, while interesting, immunofluorescence results are limited by the lack of statistical significance and were performed with markers that can be attributed to other cell types (CD8 + by dendritic cells or NK cells, and CD4 + by monocytes).…”

Animal Models for Heart Transplantation Focusing on the Pathological Conditions

“…First, the recipient's left internal carotid artery was replaced with a donor carotid artery, and heterotopic abdominal heart transplantation was performed [22]. Then, a heart and abdominal aorta transplantation was performed heterotopically [23]. Because CAV is associated with acute cardiac parenchymal rejection after transplantation, combined aorta/carotid artery allograft and heart allograft transplantation may result in more significant intimal hyperplasia in CAV models and more closely resemble the actual pathological progression of CAV [22,23].…”