Vascularized Allograft Transplantation Research Articles

The Value of Upper Extremity, face, and uterus transplantation: A Summit Conference

A panel of over 60 experts in the field of vascular composite allotransplantation from around the United States gathered on November 8, 2019 at the Uniformed Services University of the Health Sciences, in Bethesda MD. Experts in the field were recruited and invited through a collaborative effort of the American Society for Reconstructive Transplantation, the American Society of Transplantation, the American Society for Reproductive Medicine, and the American Society of Transplant Surgeons in order to discuss The Value of Upper Extremity, Face, and Uterus Transplantation: A Summit Conference . All sessions were directed by a moderator and focused on indications and contraindications, outcomes and costs of vascular composite allotransplantations in order to evaluate and discuss the state of the art science in the field. Representatives of major vascular composite allotransplantation centers in North America (Cleveland Clinic, University of Pennsylvania, Brigham and Women’s Health, New York University, the Mayo Clinic, Baylor, John Hopkins University, the University of Louisville) collaborated in order to present the combined experience of the major transplant centers in the United States. The panel members developed consensus guidelines for publication demonstrating success and unity amongst the vascular composite allotransplantation and solid organ transplantation communities. • A panel of 60 vascular composite allotransplantation experts from around the United States met in Bethesda, MD on November 8, 2019. • Indications, contraindication, outcomes and complications of face, hand and uterus transplantation were discussed. • This consensus meeting served to propel the field of vascular allograft transplantation through unity.

Historical Overview of Vascular Allograft Transplantation

There is a mix of therapeutic options for revascularisation in vascular surgery. The authors performed a literature review on the evolution of vascular allograft transplantation and its use and acceptance by vascular surgeons. This review exposed three stages: the first stage involved preliminary experimentation; the second stage was a decline in use due to long-term complications, and the third stage is its current use in special indications subject to a thorough analysis. There are few indications for the use of vascular allografts in clinical guidelines. However, there are publications of long series of case studies with variable results reflecting international use of the procedure. There is a current trend that favours its use with limited and individualised indications.

B7-H1 Expression Is Required for Human Endometrial Regenerative Cells in the Prevention of Transplant Vasculopathy in Mice.

Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN-γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro. ERCs could alleviate transplant vasculopathy, as the intimal growth of transplanted aorta was limited, and the preventive effects were correlated with an increase in the percentages of CD11c+MHC class IIlowCD86low dendritic cells, CD68+CD206+ macrophages, and CD4+CD25+Foxp3+ T cells, as well as a decrease in the percentages of CD68+ macrophages, CD3+CD4+ T cells, CD3+CD8+ T cells, and donor-reactive IgM and IgG antibodies. Moreover, overexpression of B7-H1 by IFN-γ can promote the immunosuppressive effect of ERCs. These results suggest that overexpression of B7-H1 stimulated by IFN-γ is required for ERCs to prevent the transplant vasculopathy, and this study provides a theoretical basis for the future clinical use of human ERCs.

Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho-Associated Kinases Expression.

Objective. Transplant arteriosclerosis is considered one of the major factors affecting the survival time of grafts after organ transplantation. In this study, we proposed a hypothesis of whether lycopene can protect grafted vessels through regulating key proteins expression involved in arteriosclerosis. Methods. Allogeneic aortic transplantation was performed using Brow-Norway rats as donors and Lewis rats as recipients. After transplantation, the recipients were divided into two groups: the allograft group and the lycopene group. Negative control rats (isograft group) were also established. Histopathological staining was performed to observe the pathological changes, and the expression levels of Ki-67, caspase-3, Rho-associated kinases, intercellular adhesion molecules (ICAM-1), and eNOS were assessed. Western blotting analysis and real-time PCR were also performed for quantitative analysis. Results. The histopathological staining showed that vascular stenosis and intimal thickening were not evident after lycopene treatment. The Ki-67, ROCK1, ROCK2, and ICAM-1 expression levels were significantly decreased. However, eNOS expression in grafted arteries and plasma cGMP concentration were increased after lycopene treatment. Conclusions. Lycopene could alleviate vascular arteriosclerosis in allograft transplantation via downregulating Rho-associated kinases and regulating key factor expression through the NO/cGMP pathways, which may provide a potentially effective method for transplant arteriosclerosis in clinical organ transplantation.

Survival of microvascular physeal allograft transplants following withdrawal of short-term postoperative immunosuppression.

Physeal necrosis following vascularized allograft transplantation occurs because of vascular rejection. The effect of immunosuppression withdrawal on physeal viability after bone-healing to the recipient site was investigated with use of a validated model for heterotopic microvascular transplantation of rabbit tibial physeal allografts. Our hypothesis was that an allograft survives after withdrawal of immunosuppression only if bone-healing, and therefore epiphyseal and metaphyseal vascular continuity, occurs between the transplanted physis and the recipient bone. Physeal grafts with adjacent exposed epiphyseal and metaphyseal bone were transplanted to allogeneic recipients. Graft circulation was restored microsurgically. The immunosuppression regimen consisted of cyclosporine, administered for six weeks, followed by withdrawal of immunosuppression for four weeks. The animals were killed at ten weeks postoperatively. Group I consisted of twelve allografts that were transferred with bone contact between the transplanted graft and the iliac crest recipient site, whereas group II consisted of twelve allografts transplanted without bone contact. Control groups had identical surgical procedures without immunosuppression. Longitudinal growth was assessed by fine-detail radiography, and osseous union was evaluated histologically. Transplanted physes were evaluated histologically, and cellular viability was quantified by bromodeoxyuridine uptake. Two-way analysis of variance was used to compare physeal viability between groups. Following immunosuppression withdrawal, the physeal grafts with bone contact had significantly greater viability indices (16.0 +/- 2.9 compared with 0.0 +/- 0.0, p < 0.005) and decreased longitudinal growth (5.1 +/- 1.9 mm compared with 10.3 +/- 3.5 mm, p < 0.05), and they demonstrated histological features that were consistent with continued viability associated with mild rejection compared with grafts transplanted without bone contact. Abnormalities of physeal architecture, however, were seen routinely. All control physes transferred without immunosuppression were nonviable and did not grow. The viability of physeal allograft transplants is preserved following the withdrawal of immunosuppression, provided that the graft design and recipient site preparation allow for epiphyseal and metaphyseal neovascularization mediated by bone-healing between graft and recipient.