Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biomed Res Int. 2013;2013:796046. doi: 10.1155/2013/796046. Epub 2013 Oct 9.

MHC universal cells survive in an allogeneic environment after incompatible transplantation.

Author information

  • 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.
  • 4Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany ; German Red Cross, Blood Services NSTOB, Institute Springe, Lower Saxony, 31832 Springe, Germany.

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(l)) (RT1-A(l)) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1(l)) and MHC-congenic LEW.1W rats (RT1(u)), 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-1 α , IL-1 β , 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.

PMID:
24350288
[PubMed - indexed for MEDLINE]
PMCID:
PMC3856147
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Hindawi Publishing Corporation Icon for PubMed Central
    Loading ...
    Write to the Help Desk