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Clinical and Developmental Immunology
Volume 2013, Article ID 495212, 7 pages
Review Article

Site-Specific Immunosuppression in Vascularized Composite Allotransplantation: Prospects and Potential

1Department of Plastic and Reconstructive Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
2Disciplina de Cirurgia Plástica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04024-900, Brazil
3Division of Plastic and Hand Surgery, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
4Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA
5Research Center for Translational Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China
6Pittsburgh Reconstructive Transplantation Program, Department of Plastic Surgery, 3550 Terrace Street, Pittsburgh, PA 15261, USA

Received 2 July 2012; Accepted 18 January 2013

Academic Editor: Gerald Brandacher

Copyright © 2013 Jonas T. Schnider et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Skin is the most immunogenic component of a vascularized composite allograft (VCA) and is the primary trigger and target of rejection. The skin is directly accessible for visual monitoring of acute rejection (AR) and for directed biopsy, timely therapeutic intervention, and management of AR. Logically, antirejection drugs, biologics, or other agents delivered locally to the VCA may reduce the need for systemic immunosuppression with its adverse effects. Topical FK 506 (tacrolimus) and steroids have been used in clinical VCA as an adjunct to systemic therapy with unclear beneficial effects. However, there are no commercially available topical formulations for other widely used systemic immunosuppressive drugs such as mycophenolic acid, sirolimus, and everolimus. Investigating the site-specific therapeutic effects and efficacy of systemically active agents may enable optimizing the dosing, frequency, and duration of overall immunosuppression in VCA with minimization or elimination of long-term drug-related toxicity.