Open AccessImmunogenicity of allogeneic mesenchymal stem cells
Author(s) -
Schu Sabine,
Nosov Mikhail,
O'Flynn Lisa,
Shaw Georgina,
Treacy Oliver,
Barry Frank,
Murphy Mary,
O'Brien Timothy,
Ritter Thomas
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01509.x
Subject(s) - cytotoxic t cell , immunogenicity , mesenchymal stem cell , immune system , in vivo , downregulation and upregulation , immunology , biology , il 2 receptor , cancer research , in vitro , microbiology and biotechnology , t cell , biochemistry , gene
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, MSC s 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 CD 25 and CD 71 as well as downregulation of CD 62L on CD 4 + 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.