Placenta-Derived Decidual Stromal Cells for Graft-Versus-Host Disease, Hemorrhaging, and Toxicity after Allogeneic Hematopoietic Stem Cell Transplantation

Mesenchymal stem cells (MSCs) may cure life-threatening acute GVHD, but long-term survival has been unsatisfactory. The placenta protects the fetus from the mother’s immune system, and placental tissues have been used for over 100 years in Africa to successfully treat burn injuries. Decidual stromal cells (DSCs) are accessable without any invasive procedure, with little or no need for ethical considerations, as the placenta is normally discarded after delivery. We isolate, culture, expand, and store DSCs from term placentas. They have fundamental differences to MSCs. DSCs do not differentiate as well to bone or cartilage. DSCs need cell-to-cell contact to be immunosuppressive and to induce FoxP3 regulatory T-cells. Blocking of the activity of IDO, prostaglandin E2, PD-L1, and interferon impairs the immunosuppressive capacity of DSCs in MLC. Human DSCs inhibit MLC in mice. MCSs and DSCs induce xenoreactivity.

In culture, DSCs can be expanded appreciably, and from one placenta we can obtain enough cells to treat more than 20 patients. With early treatment (within median six days) of steroid refractory acute GVHD, one-year survival was 73%—as opposed to 6% in retrospective controls not treated with stromal cells (p<0.001). A partial response was seen in two of three patients with severe chronic GVHD. Twelve patients have been treated for hemorrhagic cystitis, and now we have proceeded with a prospective double-blind randomized study. A 33-year-old man developed acute respiratory distress syndrome (ARDS) after septicemia and ASCT. He required 15 L/min oxygen by mask. After infusion of 1 × 10⁶ DSCs, oxygen saturation increased instantly from 92% to 98%; requirement for oxygen decreased, and it was discontinued after five days. Chest radiography improved and elevations in cytokines/chemokines, G-CSF, IL-6, IL-8, MCP-1, and TNF-alfa decreased. The patient is now alive and well eight months after ASCT. We reversed paresis in the arms and legs (respectively) of two patients with polyneuropathies. The first patient had recurrence of paresis and needed two additional infusions of DSCs. The second patient has no symptoms four months after infusion. Altogether, we have treated 59 patients with 136 doses of DSCs and we have not seen any acute side effects.

To conclude, DSCs are an effective therapy for acute and chronic GVHD, hemorrhagic cystitis, ARDS, and neuropathy. So far, we have not seen any side effects.