Peer-Reviewed Journal Details
Mandatory Fields
Alagesan, S,Sanz-Nogues, C,Chen, XZ,Creane, M,Ritter, T,Ceredig, R,O'Brien, T,Griffin, MD
2018
May
Immunol Cell Biol
Anti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells
Published
Optional Fields
Antibodies cell therapy immunogenicity immunosuppression mesenchymal stromal cells vascular disease CRITICAL LIMB ISCHEMIA STEM-CELLS IN-VIVO THERAPEUTIC PROPERTIES BUERGERS-DISEASE TRANSPLANTATION MECHANISMS DIFFERENTIATION IMMUNOGENICITY REJECTION
96
536
548
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice 2 weeks after single or repeated IM injections of fully mismatched-MHC allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline. In mice subjected to hind limb ischemia (HLI), anti-donor IgG was analyzed following IM allo-MSC injection with and without administration of the T-cell immunosuppressant tacrolimus. Recipients of single and repeated IM allo-MSC developed readily-detectable anti-donor IgG. Serum anti-donor IgG levels were similar to those of allo-splenocyte recipients but had higher IgG1/IgG2a ratio and variable capacity for complement-mediated lysis of donor cells. The induced anti-donor IgG bound readily to allo-MSC and this binding was increased following allo-MSC pretreatment with interferon gamma. In mice with HLI, IM injection of allo-MSC into the ischemic limb was also associated with induction of anti-donor IgG but this was abrogated by tacrolimus (FK-506). The results indicate that allo-MSC are inherently immunogenic when delivered intramuscularly to healthy and ischemic mouse hind limb, but induce an IgG1-skewed humoral response that is suppressed by tacrolimus.
10.1111/imcb.12024
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