Int Immunopharmacol. 2020 May 8;84:106541. doi: 10.1016/j.intimp.2020.106541. [Epub ahead of print]

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.

Guo L¹, Lai P¹, Wang Y¹, Huang T², Chen X¹, Geng S¹, Huang X¹, Luo C¹, Wu S¹, Ling W¹, Huang L¹, Du X³, Weng J⁴.

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.