Immunology of Vascularized Composite Allografts

Copyright © 2013 Gerald Brandacher 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. Over the past decade, vascularized composite allotransplan-tation (VCA), such as hand and face transplantation, has become a clinical reality and a viable treatment option for those patients suffering from complex tissue injuries or defects not amenable to conventional reconstruction. Despite the fact that early and intermediate functional outcomes are highly encouraging rejection and the need for chronic immunosuppressive treatment continue to be the bane of VCA, preventing its broader clinical application. A thorough understanding of the mechanisms underlying alloimmune responses in VCA is key to establish novel protocols for immunomodulation and tolerance induction after this type of transplant, without the need for long-term immunosuppression. Such advances would diminish the risks and favor the benefits for these non-life-saving but life-changing transplants. This special issue is devoted to the immunology of vascularized composite allografts. The individual authors are leaders in the field, with extensive knowledge and expertise in this novel and emerging field of transplantation. The goal of this issue is to cover various specific aspects, as well as some of the immunological challenges related to VCA. The main focus is on tolerance strategies and how those apply to VCA. Greater scrutiny is applied to immunosuppression-induced complications in VCA recipients compared to solid organ transplant patients since VCA is deemed life-enhancing rather than life-saving interventions. K. V. Ravin-dra et al. discuss the pressure to develop tolerance-inducing strategies in VCA. D. A. Leonard et al. provide a comprehensive review of the use of mixed chimerism approaches for tolerance induction in the field of VCA with a particular emphasis on translational large animal (MGH miniature swine) protocols. The authors also provide an interesting overview of novel cellular therapies , such as regulatory T cells, regulatory dendritic cells, or mesenchymal stem cells as potential adjuvants to mixed hematopoietic chimerism in the development of tolerance induction protocols for clinical VCA. M. Siemionow and A. Klimczak discuss the Cleveland Clinic research experience with chimerism-based experimental small animal models for tolerance induction and highlight in particular the complexity of immunomodulatory protocols in VCA as well as their relevance and applicability for clinical practice. W.-C. Huang et al. review approaches to improve the safety of tolerance inducing regimes currently applied to VCA …