Immunological mechanisms underlying the novel application of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in graft-versus-host disease (GvHD) therapy.

A serious side effect of allogeneic hematopoietic cell transplantation (HCT) is known as graft-versus-host disease (GvHD), in which the recipient's body is attacked by donor immune cells, leading to a high rate of morbidity and death. Although there are several therapies available for GvHD, their efficacy is limited, and they sometimes have serious adverse effects. Recently, one of the most interesting research in the field of cell therapy is the use of mesenchymal stromal cells (MSCs), which have been investigated in the treatment of HCT and its consequences such as GvHD, due to their potential in tissue repair and immunomodulatory activities. The potential negative consequences of direct cell transplantation are avoided by using MSC-EVs, which are micro vesicles packed with physiologically active materials like proteins, microRNAs, and other nucleic acids. One of the biggest advantages of MSC-EVs is their ability to dramatically alter immune cell responses in GvHD by delivering immunomodulatory chemicals and anti-inflammatory drugs to recipient cells. Some of the significant discoveries include encouraging the differentiation of pro-inflammatory macrophages into tissue-reparative macrophages, inhibiting the generation of inflammatory cytokines, and improving the function of regulatory T-cells. This study details the effects of MSC-EVs on the multiple alterations that occurred inside host cells as well as immunomodulation mediated by both T cells and antigen-presenting cells in terms of the immunopathology of GvHD and direct regenerative effects on damaged tissues.