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 graft-versus-host 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.
Tisato
V
V
Stem Cell Biology Section, Kennedy Institute of Rheumatology, Imperial College, London, UK.
Naresh
K
K
Girdlestone
J
J
Navarrete
C
C
Dazzi
F
F
D000818:Animals; D002455:Cell Division; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014183:Transplantation, Heterologous