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

Int Immunopharmacol. 2020 Jul:84:106541. doi: 10.1016/j.intimp.2020.106541. Epub 2020 May 18.

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.

Keywords: Chronic graft-versus-host-disease; Extracellular vesicles; Immunoregulation; Macrophage; Mesenchymal stem cells.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Chronic Disease
  • Disease Models, Animal
  • Extracellular Vesicles / immunology*
  • Female
  • Fibrosis
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Macrophages / immunology*
  • Mesenchymal Stem Cells*
  • Mice, Inbred BALB C
  • Skin / pathology
  • Skin Diseases / immunology*
  • Skin Diseases / pathology
  • Umbilical Cord / cytology