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

作者：Guo, Liyan; Lai, Peilong; Wang, Yulian; Huang, Tian; Chen, Xiaomei; Geng, Suxia; Huang, Xin; Luo, Chenwei; Wu, Suijing; Ling, Wei; Huang, Lisi; Du, Xin^*; Weng, Jianyu^*

来源：International Immunopharmacology, 2020, 84: 106541.

DOI：10.1016/j.intimp.2020.106541

• Extracellular vesicles
• Chronic graft-versus-host-disease
• Mesenchymal stem cells
• Immunoregulation
• Macrophage

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-beta 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.

• 单位
  广东省人民医院