1. ¹Stem Cell Biology Section, Kennedy Institute of Rheumatology, Imperial College, London, UK
2. ²Department of Histopathology, Hammersmith Hospital, Imperial College, London, UK
3. ³H&I Research Department, Histocompatibility and Immunogenetics Research Group, Colindale Centre National Health Service Blood and Transplant, Colindale, UK

Correspondence: Professor F Dazzi, Faculty of Medicine, Department of Haematology, Hammersmith Campus, Imperial College, Du Cane Road, London W12 0NN, UK. E-mail: f.dazzi@imperial.ac.uk

Received 5 May 2007; Revised 22 May 2007; Accepted 24 May 2007; Published online 12 July 2007.

Abstract

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.