Background Mesenchymal stem cells (MSC) have immunomodulatory effects. The aim was to study the effect of MSC infusion on graft-versus-host disease (GVHD). Methods We gave MSC to eight patients with steroid-refractory grades III-IV GVHD and one who had extensive chronic GVHD. The MSC dose was median 1.0 (range 0.7 to 9)x10(6)/kg. No acute side-effects occurred after the MSC infusions. Six patients were treated once and three patients twice. Two patients received MSC from HLA-identical siblings, six from haplo-identical family donors and four from unrelated mismatched donors. Results Acute GVHD disappeared completely in six of eight patients. One of these developed cytomegalovirus gastroenteritis. Complete resolution was seen in gut (6), liver (1) and skin (1). Two died soon after MSC treatment with no obvious response. One of them had MSC donor DNA in the colon and a lymph node. Five patients are still alive between 2 months and 3 years after the transplantation. Their survival rate was significantly better than that of 16 patients with steroid-resistant biopsy-proven gastrointestinal GVHD, not treated with MSC during the same period (P = 0.03). One patient treated for extensive chronic GVHD showed a transient response in the liver, but not in the skin and he died of Epstein-Barr virus lymphoma. Conclusion MSC is a very promising treatment for severe steroid-resistant acute GVHD.

Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease.

Cytokine dysregulation and acute graft-versus-host disease.

The development of nuclear arms at the end of World War II was a major stimulus for research into radiation damage to the hematopoietic system and into the treatment of such damage through bone marrow transplantation [1]. A large body of research with mice, dogs, and monkeys established a “bone marrow syndrome” with death through the complications of pancytopenia after a total body dose of 5–7 Gy (500–700 rad). Such animals could be salvaged by the infusion of syngeneic bone marrow [2] or allogeneic bone marrow [3,4]. These studies were trailblazers for bone marrow transplantation as therapeutic modality in man.

Graft-Versus-Host Disease

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved into an effective adoptive cellular immunotherapy for the treatment of a number of cancers. The immunobiology of allogeneic HSCT is unique in transplantation in that it involves potential immune recognition and attack between both donor and host. Much of the immunobiology of allogeneic HSCT has been gleaned from preclinical models and correlation with clinical observations. We review our current understanding of some of the issues that affect the success of this therapy, including host-versus-graft (HVG) reactions, graft-versus-host disease (GVHD), graft-versus-tumor (GVT) activity, and restoration of functional immunity to prevent transplant-related opportunistic infections. We also review new strategies to optimize the GVT and improve overall immune function while reducing GVHD and graft rejection.

Immunobiology of Allogeneic Hematopoietic Stem Cell Transplantation

Immunobiology of Human Mesenchymal Stem Cells and Future Use in Hematopoietic Stem Cell Transplantation

Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10)

A monoclonal antibody against the IL2-Receptor (B-B10) has been developed which inhibits activated T cells. Large batches of B-B10 have been purified from ascites and were checked for the absence of endotoxins, murine DNA and virus before being released for clinical use. Thirty-two patients with corticosteroid-resistant acute Graft versus Host Disease have been treated with B-B10. No side effects were observed and 68% of the patients showed full response to treatment.

A semi-pharmaceutical approach for the preparation of an anti-IL2 receptor monoclonal antibody in the treatment of acute GvHD in a multicentric study.

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Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10)

A semi-pharmaceutical approach for the preparation of an anti-IL2 receptor monoclonal antibody in the treatment of acute GvHD in a multicentric study.