Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response

Abstract Objective To illustrate the potential effects and mechanism of extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) on fibrosis in sclerodermatous chronic graft-versus-host-disease (cGVHD) models after allogeneic hematopoietic stem cell transplantation. Methods We first observed the therapeutic effects of MSC-EVs on a minor histocompatibility haploidentical model of sclerodermatous cGVHD and the function of MSC-EVs on skin fibrosis and macrophage activation and the related pro-fibrosis protein. Additionally, we observed the effects of MSC-EVs on B cells, the T follicular helper cell (TFH) and germinal center B cell (GC B cells) interaction and the ratio of B cell activation factor (BAFF) to B cells in vivo. Results MSC-EVs treatment could alleviate the cGVHD scores and fibrosis of skin in sclerodermatous cGVHD mice, and this was associated with a reduction macrophage percentage in the skin and spleen, and a reduction in macrophage infiltration and TGF-β and smad2 production in the skin. Additionally, MSC-EVs influence B cells immune response by blocking the TFH/GC B cells interaction and reducing the ratio of BAFF to B cells in vivo. Conclusion MSC-EVs prevent the fibrosis of sclerodermatous cGVHD mouse model by suppressing the activation of macrophages and B cells immune response.