Mesenchymal stem cells for treatment of acute and chronic graft-versus-host disease, tissue toxicity and hemorrhages

Abstract

Mesenchymal stem cells (MSCs) have immunomodulatory effects and low immunogenicity. MSCs inhibit T-cell alloreactivity in vitro. Immune inhibition is caused by soluble factors. MSCs affect almost all cells of the immune system. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. We treated patients with life-threatening acute graft-versus-host disease (GVHD) not responding to conventional immunosuppressive therapy with MSCs. Approximately half of the patients responded. HLA-identical or third party MSCs were equally effective. Children tended to have a better response compared to adults. MSCs have also been used for chronic GVHD with positive effects. MSCs also reversed tissue toxicity such as hemorrhagic cystitis, pneumomediastinum and colon perforation with peritonitis. A patient with extensive hemorrhages was successfully treated with repeated doses of MSCs pooled from two donors. This may indicate that MSCs apart from wound healing may stimulate clotting and vasoconstriction. To conclude, MSCs is a novel treatment that may be used for GVHD, tissue toxicity and hemorrhages because of its immune inhibitory and anti-inflammatory effects.