Anti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells

Immunol Cell Biol. 2018 May;96(5):536-548. doi: 10.1111/imcb.12024. Epub 2018 Mar 23.


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.

Keywords: Antibodies; cell therapy; immunogenicity; immunosuppression; mesenchymal stromal cells; vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Dependent Cell Cytotoxicity
  • Cells, Cultured
  • Histocompatibility Antigens / immunology
  • Immunity, Humoral
  • Immunosuppressive Agents / administration & dosage
  • Injections, Intramuscular
  • Ischemia / immunology*
  • Isoantigens / immunology*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Tacrolimus / administration & dosage*
  • Tissue Donors
  • Transplantation, Homologous


  • Histocompatibility Antigens
  • Immunosuppressive Agents
  • Isoantigens
  • Tacrolimus