Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease

The immunosuppressive properties of mesenchymal stem cells ( MSC) make them particularly attractive to manipulate graftversushost disease ( GVHD). So far, the experience of using MSC to treat GVHD is limited to a few cases, controversial results come from preclinical models and several issues remain to be clarified. The present studies were designed to address these questions in a xenogenic model testing the ability of umbilical cord blood- derived MSC ( UCB- MSC) to prevent and/ or treat GVHD. Sublethally irradiatiated non- obese diabetic/ severe combined immunodeficiency NOD/ SCID mice transplanted with human peripheral blood mononuclear cells ( huPBMC) showed extensive human T- cell proliferation in the peripheral blood, lymphoid and non- lymphoid tissues, which evolved in extensive GVHD ( wasting, ruffled hair and hunched back). The mice treated with a single dose of UCB- MSC did not behave differently form the controls. However, when UCB- MSC were given at weekly intervals, there was a marked decrease in human T- cell proliferation and none of the mice developed GVHD. No therapeutic effect was obtained if UCB- MSC were administered at onset of GVHD. This work supports the clinical use of MSC in stem cell transplantation as a prophylaxis rather than treatment of GVHD.