Mesenchymal Stromal Cells and Graft-versus-Host Disease: Preclinical and Clinical Studies

Graft-versus-host disease (GVHD) remains one of the most severe complications following allogeneic hematopoietic stem cell transplantation (HSCT), significantly contributing to transplant-related morbidity and mortality. While systemic corticosteroids are the standard first-line therapy, a substantial proportion of patients develop steroid-refractory GVHD, which is associated with poor clinical outcomes. Mesenchymal stromal cells (MSCs), a heterogeneous population of multipotent stromal cells derived from diverse tissue sources, have garnered increasing attention due to their immunomodulatory capacity and ability to promote tissue repair. Preclinical studies and early-phase clinical trials have demonstrated the potential of MSCs to enhance hematopoietic engraftment, reduce the incidence and severity of GVHD, and improve immune homeostasis. Encouraging data, particularly in the treatment of steroid-resistant acute GVHD, suggest a favorable safety profile and therapeutic efficacy. In this review, we comprehensively summarize the current understanding of MSCs biology, preclinical evidence, and clinical applications in the context of GVHD, and we further discuss emerging strategies for optimizing MSC-based therapies to enhance their clinical utility.