Potential and challenges of placenta-derived decidua stromal cell therapy in inflammation-associated disorders

Decidual stromal cells (DSCs) isolated from maternal part of placenta, like mesenchymal stromal cells (MSCs), are able to inhibit alloreactivity in-vitro but in a superior way which makes them an attractive alternative for anti-inflammatory therapies. In alloreactivity, when a strong immune response is developed against alloantigens, DSCs develop an anti-inflammatory environment, both through cell-to-cell contact and soluble factors, to prevent the adverse effects of alloantigens. In alloreactivity-associated inflammation, proinflammatory cytokines can be released and then involved in the up-regulation of inflammatory reactions which is one of the main causes of inflammatory related disorders. According to the preclinical and clinical studies, DSCs could be promising alternatives for the treatment of inflammatory-related diseases for which no definitive and successful treatment has been found yet. Here we first present the DSCs functions in creating the anti-inflammatory environment, their immunomodulatory effects, and their advantages over MSCs. Then, preclinical and clinical studies using DSCs for treatment of inflammatory disease including: graft-versus-host-disease (GVHD) after allogeneic hematopoi-etic stem cell transplantation (Allo-HSCT), COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) and in particular, Infertility-related disorders, are presented. Finally, the challenges of using DSCs in clinical settings will be described.