Assessment of Vedolizumab and UC-MSC interaction and therapeutic potential in acute graft-versus-host-disease.

Acute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation, characterized by donor T-cell-mediated immune responses against the host. This condition significantly impacts patient quality of life, and it is associated with mortality, particularly when the gastrointestinal tract is affected. This study investigated the potential therapeutic synergy between umbilical cord-derived mesenchymal stromal cells (UC-MSCs), known for their immunomodulatory potential, and Vedolizumab (VDZ), a gut-specific α4β7 integrin antagonist that prevents lymphocyte trafficking to intestinal tissues. Our results demonstrate that UC-MSCs maintain an unaltered immunophenotype and low α4β7 expression in the presence of VDZ, even under inflammatory conditions. Moreover, VDZ exposure did not modify UC-MSC immunomodulatory functions, IDO expression, or susceptibility to peripheral blood mononuclear cell-mediated lysis. In an NSG mouse model of aGvHD, single-agent therapies showed limited effects on survival, whereas combined VDZ and UC-MSCs highlighted the critical importance of optimizing administration windows and dosing schedules. Although no clear synergistic therapeutic benefits were observed in this model, the absence of toxicity or mutual inhibition establishes a favorable safety profile for the combination of VDZ and UC-MSCs as rescue therapy for steroid-refractory aGvHD. These findings also provide a rationale for exploring this combination in a prophylactic setting, preventing gastrointestinal aGvHD by limiting early lymphocyte trafficking while preserving systemic immune regulation.