Stem cell therapy for GVHD

Graft-versus-host disease (GVHD) is a major complication associated with morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). GVHD can be fatal, as patients frequently fail to respond to conventional immunosuppressants and no established second-line therapy is available. Stem cells have emerged as a therapeutic approach in a range of medical fields, including regenerative medicine, cancer, autoimmune diseases, and inflammatory diseases, because of their unique properties. In particular, mesenchymal stem cells (MSCs) have created increasing interest as a therapeutic agent for various immunemediated diseases including GVHD. MSCs demonstrate therapeutic potential by exerting potent immunosuppressive effects through interactions between lymphocytes associated with both the innate and adaptive immune system. Preclinical experiments using MSCs for the treatment of GVHD have provided critical insights into the mechanism of action of MSCs and evidence for clinical translation. In the clinical setting, Ringden's pilot study using MSCs to treat a steroidrefractory GVHD pediatric patient was a milestone in the field of MSC therapy, which leads to numerous worldwide studies on steroid-refractory GVHD, de novo GVHD, chronic GVHD treatment, and GVHD prevention. In this chapter, we focus on the recent advances of MSCs for the treatment of GVHD in both preclinical and clinical settings. We discuss the current limitations and highlight the future considerations that should be made when using stem cell therapy for GVHD.