Mesenchymal stem cell-derived exosomes for managing graft-versus-host disease: An updated view.

Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD, a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysregulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluid-like structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-γ and TNF-α by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD.