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BioMed Research International
Volume 2013 (2013), Article ID 796046, 12 pages
http://dx.doi.org/10.1155/2013/796046
Research Article

MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

1Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany
2Institute for Laboratory Animal Science, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany
3Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Nordrhein-Westfalen, Germany
4German Red Cross, Blood Services NSTOB, Institute Springe, Lower Saxony, 31832 Springe, Germany

Received 10 June 2013; Revised 29 August 2013; Accepted 29 August 2013

Academic Editor: Chung-Liang Chien

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

Abstract

Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm ( ) (RT1- ) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats ( ) and MHC-congenic LEW.1W rats ( ), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine.