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 language | English |
|---|---|
| Pages (from-to) | 2615-2627 |
| Number of pages | 13 |
| Journal | Cell Transplantation |
| Volume | 24 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2015 |
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Keywords
- Extracellular vesicles(EVs)
- Immunomodulation
- Mesenchymal stem/stromal cells(MSCs)
- Regulatory T cells
ASJC Scopus subject areas
- Cell Biology
- Transplantation
- Biomedical Engineering
Cite this
Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes. / Fattore, Andrea Del; Luciano, Rosa; Pascucci, Luisa; Goffredo, Bianca Maria; Giorda, Ezio; Scapaticci, Margherita; Fierabracci, Alessandra; Muraca, Maurizio.
In: Cell Transplantation, Vol. 24, No. 12, 2015, p. 2615-2627.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes
AU - Fattore, Andrea Del
AU - Luciano, Rosa
AU - Pascucci, Luisa
AU - Goffredo, Bianca Maria
AU - Giorda, Ezio
AU - Scapaticci, Margherita
AU - Fierabracci, Alessandra
AU - Muraca, Maurizio
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Extracellular vesicles(EVs)
KW - Immunomodulation
KW - Mesenchymal stem/stromal cells(MSCs)
KW - Regulatory T cells
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U2 - 10.3727/096368915X687543
DO - 10.3727/096368915X687543
M3 - Article
VL - 24
SP - 2615
EP - 2627
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 12
ER -