Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes

Andrea Del Fattore, Rosa Luciano, Luisa Pascucci, Bianca Maria Goffredo, Ezio Giorda, Margherita Scapaticci, Alessandra Fierabracci, Maurizio Muraca

Research output: Contribution to journalArticlepeer-review

Abstract

The immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. We have recently shown that the immunosuppressive effects of MSCs on B lymphocytes in peripheral blood mononuclear cell (PBMC) culture can be reproduced by extracellular vesicles (EVs) isolated from MSC culture supernatants. Here we investigated the effect of bone marrow-derived MSC-EVs on T cells on PBMC cultures stimulated with anti-CD3/CD28 beads. Stimulation increased the number of proliferating CD3+ cells as well as of regulatory T cells (Tregs). Coculture with MSCs inhibited the proliferation of CD3+ cells, with no significant changes in apoptosis. Addition of MSC-EVs to PBMCs did not affect proliferation of CD3+ cells, but induced the apoptosis of CD3+ cells and of the CD4+ subpopulation and increased the roliferation and the apoptosis of Tregs. Moreover, MSC-EV treatment increased the Treg/Teff ratio and the immunosuppressive cytokine IL-10 concentration in culture medium. The activity of indoleamine 2,3-dioxygenase (IDO), an established mediator of MSC immunosuppressive effects, was increased in supernatants of PBMCs cocultured with MSCs, but was not affected by the presence of MSC-EVs. MSC-EVs demonstrate immunomodulatory effects on T cells in vitro. However, these effects and the underlying mechanisms appear to be different from those exhibited by their cells of origin.

Original languageEnglish
Pages (from-to)2615-2627
Number of pages13
JournalCell Transplantation
Volume24
Issue number12
DOIs
Publication statusPublished - 2015

Keywords

  • Extracellular vesicles(EVs)
  • Immunomodulation
  • Mesenchymal stem/stromal cells(MSCs)
  • Regulatory T cells

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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