Placenta-Derived Decidual Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

We introduced mesenchymal stromal cells (MSCs) as therapy for acute GVHD with a dramatic response in some patients, but no response in others.1, 2 The placenta protects the fetus from the mother’s immune system. The placenta has also been used for hundred years to treat burn injuries in Africa. Decidual stromal cells (DSCs) differ from bone marrow-derived (BM) MSCs in greater expansion potential, being half the size, less differentiation capacity to bone or cartilage, and need direct contact with T-cells to inhibit alloreactivity in vitro. In a pilot study, we found that DSCs are immunosuppressive and may cure life-threatening acute GVHD.3 Thirty-six patients were treated with DSCs for severe or steroid-refractory gastrointestinal acute GVHD. The first 17 patients received DSCs dissolved in saline with 5% AB-plasma and all had grade III acute GVHD (DSC group 1). Twenty-one patients were treated with DSCs dissolved in saline with 5% albumin and repeated doses, six had grade II and 15 had grade III acute GVHD (DSC group 2). We included 32 retrospective controls, nine with grade II and 23 with grade III acute GVHD who were not treated with stromal cells. All patients received prednisolone 2 mg/kg/day. Median age in the controls, DSC group 1 and DSC group 2, were 40 (range 3-67), 53 (0.8-65), and 48 (1.3-72.2), respectively. Three patients had transient reactions during DSC infusions. Three patients had zygomycetes infection, three had graft failure and two squamous cell carcinoma. Such events will be elucidated with more patients. Causes of deaths, excluding GVHD, were the same in the DSC patients and the controls. The response rates, no response/partial response/complete response was 24/6/2 in the controls, 7/5/5 in the DSC group 1 and 0/10/11 in the DSC group 2. One-year survival was 3% in the controls, 47% in DSC group 1 and 75% in the DSC group 2 (p<0.01 vs. controls). The DSC group 2 also had a better one-year survival, as opposed to 23% among 22 patients treated with BM-MSC (p<0.01). Median steroid dose at four weeks after initiation of steroids was 1.67 mg/kg in the controls, 0.7 mg/kg in the DSC group 1, and 0.57 mg/kg in the DSC group 2. Serum albumin, which was decreased at initiation of therapy increased among patients in DSC group 2 (p<0.01). We conclude that DSCs is a promising treatment for severe and/or steroid-refractory acute GVHD. 1. Le Blanc K, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439.2. Ringden O, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81: 1390.3. Ringden O, et al. Fetal membrane cells for treatment of steroid-refractory acute graft-versus-host disease. Stem cells 2013; 31: 592.