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Placenta-derived Decidua Stromal Cells: A New and Improved Means to Treat GVHD?

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Review of “Placenta-derived decidua stromal cells for treatment of severe acute graft-versus-host disease” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Graft-versus-host disease (GVHD) represents a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT) in patients suffering from advanced leukemias and severe hematological and metabolic diseases. Mesenchymal stem cell (MSC) therapy arose as a promising means to modulate immune responses and palliate GVHD; however, studies have suggested no substantial influence of MSCs on long-term overall survival [1, 2].

Now, new research from the laboratory of Olle Ringdén (Karolinska Institutet, Sweden) sought to assess the potential for placenta-derived decidua stromal cells (DSCs) as a treatment for severe acute GVHD given their stronger immunomodulatory abilities [3, 4]. The results of their pilot study, published recently in STEM CELLS Translational Medicine, suggest that DSC therapy represents a promising new strategy to fight GVHD and encourages the organization of prospective randomized trials [5].

The trial procedures and outcomes included:

 

  • Treatment of 38 patients with severe acute GVHD after HSCT with infusions of DSCs derived from term placentas between 2011 and 2015
    • 25 patients were refractory to immunosuppression by steroid-treatment, the first-line therapy in both acute and chronic GVHD
    • DSCs thawed and infused in buffer containing 5% albumin displayer higher viability than cells suspended in buffer supplemented with 10% AB blood plasma
  • Group 1 patients received fewer infusions of a higher dosage of DSCs at a lower passage number when compared to Group 2 patients
    • From 17 patients in Group 1, seven showed no response, five a partial response, and five a complete response to treatment (7/5/5)
    • From 21 patients in Group 2, ten showed a partial response and eleven a complete response to treatment (0/10/11)
  • This difference in cell viability and responses correlated to a greater one-year survival in Group 2 patients (76%) when compared to Group 1 patients (47%)
    • In steroid-refractory patients, Group 2 patients had a one-year survival rate of 73%, much greater than 31% for the Group 1 patients, 20% for BM-MSC treated patients, or 3% in historical controls

 

DSCs protect the fetus from the mother’s immune system, and this new study suggests that following an optimized procedure, DSCs could represent a new and improved means to treat GVHD. Further prospective randomized trials to evaluate efficacy may lie ahead, so stay tuned to the Stem Cells Portal to discover more about the exciting potential of placenta-derived DSCs and more stem cells treatments for GVHD!

References

  1. Remberger M and Ringden O, Treatment of severe acute graft-versus-host disease with mesenchymal stromal cells: a comparison with non-MSC treated patients. Int J Hematol 2012;96:822-4.
  2. von Bahr L, Sundberg B, Lonnies L, et al., Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 2012;18:557-64.
  3. Karlsson H, Erkers T, Nava S, et al., Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro. Clin Exp Immunol 2012;167:543-55.
  4. Ringden O, Erkers T, Nava S, et al., Fetal membrane cells for treatment of steroid-refractory acute graft-versus-host disease. Stem Cells 2013;31:592-601.
  5. Ringden O, Baygan A, Remberger M, et al., Placenta‐Derived Decidua Stromal Cells for Treatment of Severe Acute Graft‐Versus‐Host Disease. STEM CELLS Translational Medicine 2018;7:325-331.