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Immunogenicity of allogeneic mesenchymal stem cells
Mesenchymal stem cells (MSCs) inhibit proliferation of allogeneic T cells and express low levels of major histocompatibility complex class I (MHCI), MHCII and vascular adhesion molecule-1 (VCAM-1). We investigated whether their immunosuppressive properties and low immunophenotype protect allogeneic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822979/ https://www.ncbi.nlm.nih.gov/pubmed/22151542 http://dx.doi.org/10.1111/j.1582-4934.2011.01509.x |
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author | Schu, Sabine Nosov, Mikhail O'Flynn, Lisa Shaw, Georgina Treacy, Oliver Barry, Frank Murphy, Mary O'Brien, Timothy Ritter, Thomas |
author_facet | Schu, Sabine Nosov, Mikhail O'Flynn, Lisa Shaw, Georgina Treacy, Oliver Barry, Frank Murphy, Mary O'Brien, Timothy Ritter, Thomas |
author_sort | Schu, Sabine |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) inhibit proliferation of allogeneic T cells and express low levels of major histocompatibility complex class I (MHCI), MHCII and vascular adhesion molecule-1 (VCAM-1). We investigated whether their immunosuppressive properties and low immunophenotype protect allogeneic rat MSCs against cytotoxic lysis in vitro and result in a reduced immune response in vivo. Rat MSCs were partially protected against alloantigen-specific cytotoxic T cells in vitro. However, after treatment with IFN-γ and IL-1β, MSCs upregulated MHCI, MHCII and VCAM-1, and cytotoxic lysis was significantly increased. In vivo, allogeneic T cells but not allogeneic MSCs induced upregulation of the activation markers CD25 and CD71 as well as downregulation of CD62L on CD4(+) T cells from recipient rats. However, intravenous injection of allo-MSCs in rats led to the formation of alloantibodies with the capacity to facilitate complement-mediated lysis, although IgM levels were markedly decreased compared with animals that received T cells. The allo-MSC induced immune response was sufficient to lead to significantly reduced survival of subsequently injected allo-MSCs. Interestingly, no increased immunogenicity of IFN-γ stimulated allo-MSCs was observed in vivo. Both the loss of protection against cytotoxic lysis under inflammatory conditions and the induction of complement-activating antibodies will likely impact the utility of allogeneic MSCs for therapeutic applications. |
format | Online Article Text |
id | pubmed-3822979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38229792015-03-27 Immunogenicity of allogeneic mesenchymal stem cells Schu, Sabine Nosov, Mikhail O'Flynn, Lisa Shaw, Georgina Treacy, Oliver Barry, Frank Murphy, Mary O'Brien, Timothy Ritter, Thomas J Cell Mol Med Original Articles Mesenchymal stem cells (MSCs) inhibit proliferation of allogeneic T cells and express low levels of major histocompatibility complex class I (MHCI), MHCII and vascular adhesion molecule-1 (VCAM-1). We investigated whether their immunosuppressive properties and low immunophenotype protect allogeneic rat MSCs against cytotoxic lysis in vitro and result in a reduced immune response in vivo. Rat MSCs were partially protected against alloantigen-specific cytotoxic T cells in vitro. However, after treatment with IFN-γ and IL-1β, MSCs upregulated MHCI, MHCII and VCAM-1, and cytotoxic lysis was significantly increased. In vivo, allogeneic T cells but not allogeneic MSCs induced upregulation of the activation markers CD25 and CD71 as well as downregulation of CD62L on CD4(+) T cells from recipient rats. However, intravenous injection of allo-MSCs in rats led to the formation of alloantibodies with the capacity to facilitate complement-mediated lysis, although IgM levels were markedly decreased compared with animals that received T cells. The allo-MSC induced immune response was sufficient to lead to significantly reduced survival of subsequently injected allo-MSCs. Interestingly, no increased immunogenicity of IFN-γ stimulated allo-MSCs was observed in vivo. Both the loss of protection against cytotoxic lysis under inflammatory conditions and the induction of complement-activating antibodies will likely impact the utility of allogeneic MSCs for therapeutic applications. Blackwell Publishing Ltd 2012-09 2012-08-23 /pmc/articles/PMC3822979/ /pubmed/22151542 http://dx.doi.org/10.1111/j.1582-4934.2011.01509.x Text en Copyright © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
spellingShingle | Original Articles Schu, Sabine Nosov, Mikhail O'Flynn, Lisa Shaw, Georgina Treacy, Oliver Barry, Frank Murphy, Mary O'Brien, Timothy Ritter, Thomas Immunogenicity of allogeneic mesenchymal stem cells |
title | Immunogenicity of allogeneic mesenchymal stem cells |
title_full | Immunogenicity of allogeneic mesenchymal stem cells |
title_fullStr | Immunogenicity of allogeneic mesenchymal stem cells |
title_full_unstemmed | Immunogenicity of allogeneic mesenchymal stem cells |
title_short | Immunogenicity of allogeneic mesenchymal stem cells |
title_sort | immunogenicity of allogeneic mesenchymal stem cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822979/ https://www.ncbi.nlm.nih.gov/pubmed/22151542 http://dx.doi.org/10.1111/j.1582-4934.2011.01509.x |
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