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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
Repository DOI
Publication Date
2012-08-23
Keywords
mesenchymal stem cells, allo-antibody, complement, immunogenicity, 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
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Article
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Citation
Schu, Sabine; Nosov, Mikhail; O'Flynn, Lisa; Shaw, Georgina; Treacy, Oliver; Barry, Frank; Murphy, Mary; O'Brien, Timothy; Ritter, Thomas (2012). Immunogenicity of allogeneic mesenchymal stem cells. Journal of Cellular and Molecular Medicine 16 (9), 2094-2103
Abstract
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.
Funder
Publisher
Wiley-Blackwell
Publisher DOI
10.1111/j.1582-4934.2011.01509.x
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)