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Ringdén: Placenta-derived decidual stromal cells – a novel therapy for graft-versus-host disease, haemorrhages and toxicity after allogeneic haematopoietic stem cell transplantation

Allogeneic haematopoietic stem cell transplantation (ASCT) is a well-established therapy for leukaemia and other disorders of the immunohaematopoietic system. However, transplanted cells can attack the patient’s tissue, so-called graft-versus-host disease (GVHD). Severe GVHD can lead to death. Other complications after ASCT include toxicity, haemorrhages and infections.

Stromal cells, such as mesenchymal stem cells (MSCs) or placenta-derived decidual stromal cells (DSCs), have an immunosuppressive and anti-inflammatory effect. This effect is seen despite human leucocyte antigen (HLA) incompatibility between the stromal cells and stimulatory or alloreactive cells in vitro, which enables the use of third-party stromal cells in the clinic. I was the first to use MSCs for life-threatening acute GVHD with miraculous response in some, but not all, patients.

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. We isolated, cultured, expanded and stored DSCs from term placentas. DSCs differ from MSCs in that they need direct cell-to-cell contact to mediate an immunosuppressive effect and they do not differentiate as well into bone or cartilage.

To our knowledge, we are the only group which uses DSCs for clinical therapy. We have switched from MSCs to DSCs because these cells have a better immunosuppressive effect. In contrast to MSCs, DSCs are assessable without any invasive procedure and with little or no need for ethical consideration, as the placenta is normally discarded after delivery. In culture, DSCs can be produced in abundance, and from a single placenta one can get enough cells to treat more than 20 patients. Using MSCs for severe acute GVHD, the 2-year survival rate was 26% (n = 23). Using DSCs late in the treatment of advanced steroid refractory disease (n = 14), the 1-year survival rate was 39%. With earlier treatment and repeated doses (n = 13), the 1-year survival rate was 73%. This was significantly better than in steroid-refractory control patients (n = 34) not treated with stromal cells [1-year survival rate 6% (P < 0.05)]. Among three patients with severe chronic GVHD, two had a partial response after treatment with DSCs. DSCs were also successfully used for the treatment of haemorrhagic cystitis in 12 patients. Subsequently, a double-blind randomized study using DSCs or placebo has been started for haemorrhagic cystitis.

A 33-year-old male who developed acute respiratory distress syndrome, a deadly complication after septicaemia and ASCT, responded dramatically to DSC treatment and was rescued. He is now alive and well 8 months after ASCT. We reversed paresis in the arms of one patient and the legs of another patient after treatment with DSCs. Altogether, we have treated 57 patients with 132 doses of DSCs and we have not seen any acute side-effects.

To conclude, DSCs are a novel therapy that has been effective for acute and chronic GVHD, haemorrhagic cystitis, acute respiratory distress syndrome and neuropathy. In addition, this therapy might also be used for other patients with inflammation and immune reactivation in various organs, such as patients with inflammatory bowel disease, patients with rheumatological diseases and organ transplant recipients.





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