Conditioned medium from human palatine tonsil mesenchymal stem cells attenuates acute graft-vs.-host disease in mice

Abstract

Graft-vs.-host disease (GVHD) is a severe and potentially life-threatening complication of hematopoietic stem cell transplantation. Approximately 50% of patients exhibiting GVHD will not benefit from conventional steroid treatment. Although several second-line treatments are available for these patients, their prognoses remain poor due to the increased risk of infection, immunosuppression-mediated toxicity and incomplete GVHD remission, which occurs in the majority of cases. Mesenchymal stem cells (MSCs), a multipotent cell population, possess broad immunosuppressive activity and are a reportedly effective treatment of GVHD. However, the therapeutic effects of conditioned medium from MSCs on GVHD have not been demonstrated. In the present study, the efficacy of conditioned medium from human palatine tonsil-derived MSCs (T-MSC-CM) was validated against GVHD in mice. The suppressive function of T-MSC-CM on immune cell chemotaxis was confirmed in vitro. A systemic infusion of T-MSC-CM in mice with GVHD resulted in prolonged survival, rapid recovery from weight loss and reduced pathological damage in numerous GVHD-targeted organs. Furthermore, lymphocyte gene expression was significantly downregulated in GVHD mice administered T-MSC-CM. These results indicate that T-MSC-CM is a promising cellular agent to prevent or treat transplantation-associated complications such as GVHD.