IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease

David Polchert, Justin Sobinsky, G. W. Douglas, Martha Kidd, Ada Moadsiri, Eduardo Reina, Kristyn Genrich, Swati Mehrotra, Suman Setty, Brett Smith, Amelia Bartholomew

Research output: Contribution to journalArticlepeer-review

453 Scopus citations

Abstract

Graft versus host disease (GVHD), mediated by donor T cells, is a significant source of morbidity and mortality following allogeneic stem cell transplantation. Mesenchymal stem cells (MSC) can successfully treat ongoing graft versus host disease, presumably due to their ability to suppress donor T cell proliferation. Little is known about the potential of MSC to prevent GVHD. Here we show that bone marrow-isolated MSC can suppress the development of GVHD if given after donor T cell recognition of antigen. IFN-γ was required to initiate MSC efficacy. Recipients of IFN-γ-/- T cells did not respond to MSC treatment and succumbed to GVHD. MSC, pre-treated with IFN-c, became immediately active and could suppress GVHD more efficiently than a fivefold-greater number of MSC that were not activated. When given at the time of bone marrow transplantation, activated MSC could prevent GVHD mortality (100% survival, p=0.006). MSC activation was dependent on the magnitude of IFN-γ exposure, with increased IFN-γ exposure leading to increased MSC suppression of GVHD. Activated MSC present a new strategy for preventing GVHD using fewer MSC.

Original languageEnglish
Pages (from-to)1745-1755
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • GVH disease
  • IFN-γ
  • Mesenchymal stem cell

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