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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.

Hematopoietic stem cell transplantation (HSCT) is a curative option for various hematologic malignancies. However, fatal complications, such as relapse and graft-versus-host disease (GVHD) hampered favorable HSCT outcomes. Cancer cells remained in the body following the conditioning regimen, or those contaminating the autologous graft can cause relapse. Although the relapse is much lesser in allogeneic HSCT, GVHD is still a life-threatening complication in this type of HSCT. Researchers are seeking various strategies to reduce relapse and GVHD in HSCT with minimum effects on the engraftment and immune-reconstitution. Oncolytic viruses (OVs) are emerging anti-cancer agents with promising results in battling solid tumors. OVs can selectively replicate in the malignant cells in which the antiviral immune responses have defected. Hence, they could be used as a purging agent to eradicate the tumoral contamination of autologous grafts with no damages to hematopoietic stem cells. Moreover, they have been shown to alleviate GVHD complications through modulating alloreactive T cell responses. Primary results promise using OVs as a strategy to reduce both relapse and GVHD in the HSCT without affecting hematologic and immunologic engraftment. Herein, we provide the latest findings in the field of OV therapy in HSCT and discuss their pros and cons.