Peer-Reviewed Journal Details
Mandatory Fields
Schu, S;Nosov, M;O'Flynn, L;Shaw, G;Treacy, O;Barry, F;Murphy, M;O'Brien, T;Ritter, T
2012
September
Journal Of Cellular And Molecular Medicine
Immunogenicity of allogeneic mesenchymal stem cells
Published
Altmetric: 7WOS: 118 ()
Optional Fields
ACUTE MYOCARDIAL-INFARCTION PROLIFERATION IN-VITRO MARROW STROMAL CELLS VERSUS-HOST-DISEASE ACUTE-RENAL-FAILURE IMMUNE-RESPONSE CARDIAC ALLOGRAFT GENE-THERAPY NITRIC-OXIDE CALF SERUM
16
2094
2103
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-? and IL-1 beta, 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-? 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.
1582-4934
10.1111/j.1582-4934.2011.01509.x
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