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Clinical and Developmental Immunology
Volume 2013, Article ID 831410, 12 pages
http://dx.doi.org/10.1155/2013/831410
Review Article

Chimerism-Based Experimental Models for Tolerance Induction in Vascularized Composite Allografts: Cleveland Clinic Research Experience

1Department of Plastic Surgery, Cleveland Clinic, 9500 Euclid Avenue, A-60, Cleveland, OH 44195, USA
2Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland

Received 10 July 2012; Revised 12 February 2013; Accepted 12 February 2013

Academic Editor: A. W. Thomson

Copyright © 2013 Maria Siemionow and Aleksandra Klimczak. 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.

Abstract

The preclinical experimental models of vascularized composite allografts (VCAs) have been rapidly developed for the assessment of immunomodulatory protocols for clinical application. Recently, researchers have focused on immunomodulatory protocols which overcome the immunologic barrier between the allogeneic donor and recipient and may lead to tolerance induction. In order to test the feasibility of chimerism induction, experimental VCAs have been performed in different models including rodents, large animals, and nonhuman primates. These models differ in the complexity of transplanted tissue and in their responses to immunomodulatory protocols. In most applications, VCA contains multiple-tissue components; however, each individual component of CTA possesses unique immunologic characteristics that ultimately contribute to the chimerism induction and successful outcome of the VCA. Heterogenic character and complexity of tissue components in different VCA models determine the quality and robustness of donor-specific chimerism. As introduced in experimental studies, variable immunomodulatory options have been studied to achieve tolerance to VCA in rodents and large animal models allowing for widespread application in clinic. In this paper, based on our own experience, we have analyzed the current knowledge of tolerance-inducing strategies via chimerism induction in VCA experimental models in the context of immunomodulatory protocols and VCA complexity and their relevance and applicability to clinical practice.