The Immunosuppressive Effect of Mesenchymal Stromal Cells on B Lymphocytes is Mediated by Membrane Vesicles
The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer of membrane v...
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| Published in | Cell transplantation Vol. 22; no. 2; pp. 369 - 379 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Los Angeles, CA
SAGE Publications
01.02.2013
SAGE Publishing |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer of membrane vesicles, a recently recognized pathway of intercellular communication, as possible mediator of the interaction between mesenchymal stromal cells and B lymphocytes. Mesenchymal stromal cells exhibited a strong dose-dependent inhibition of B-cell proliferation and differentiation in a CpG-stimulated peripheral blood mononuclear cell coculture system. We observed that these effects could be fully reproduced by membrane vesicles isolated from mesenchymal stromal cell culture supernatants in a dose-dependent fashion. Next, we evaluated the localization of fluorescently labeled membrane vesicles within specific cell subtypes both by flow cytometry and by confocal microscopy analysis. Membrane vesicles were found to be associated with stimulated B lymphocytes, but not with other cell phenotypes (T lymphocytes, dendritic cells, natural killer cells), in peripheral blood mononuclear cell culture. These results suggest that membrane vesicles derived from mesenchymal stromal cells are the conveyors of the immunosuppressive effect on B lymphocytes. These particles should be further evaluated as immunosuppressive agents in place of the parent cells, with possible advantages in term of standardization, safety, and feasibility. |
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| AbstractList | The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer of membrane vesicles, a recently recognized pathway of intercellular communication, as possible mediator of the interaction between mesenchymal stromal cells and B lymphocytes. Mesenchymal stromal cells exhibited a strong dose-dependent inhibition of B-cell proliferation and differentiation in a CpG-stimulated peripheral blood mononuclear cell coculture system. We observed that these effects could be fully reproduced by membrane vesicles isolated from mesenchymal stromal cell culture supernatants in a dose-dependent fashion. Next, we evaluated the localization of fluorescently labeled membrane vesicles within specific cell subtypes both by flow cytometry and by confocal microscopy analysis. Membrane vesicles were found to be associated with stimulated B lymphocytes, but not with other cell phenotypes (T lymphocytes, dendritic cells, natural killer cells), in peripheral blood mononuclear cell culture. These results suggest that membrane vesicles derived from mesenchymal stromal cells are the conveyors of the immunosuppressive effect on B lymphocytes. These particles should be further evaluated as immunosuppressive agents in place of the parent cells, with possible advantages in term of standardization, safety, and feasibility. |
| Author | Budoni, Manuela Fierabracci, Alessandra Di Ciommo, Vincenzo Luciano, Rosa Petrini, Stefania Muraca, Maurizio |
| Author_xml | – sequence: 1 givenname: Manuela surname: Budoni fullname: Budoni, Manuela – sequence: 2 givenname: Alessandra surname: Fierabracci fullname: Fierabracci, Alessandra – sequence: 3 givenname: Rosa surname: Luciano fullname: Luciano, Rosa – sequence: 4 givenname: Stefania surname: Petrini fullname: Petrini, Stefania – sequence: 5 givenname: Vincenzo surname: Di Ciommo fullname: Di Ciommo, Vincenzo – sequence: 6 givenname: Maurizio surname: Muraca fullname: Muraca, Maurizio email: maurizio.muraca@opbg.net |
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| Keywords | Mesenchymal stromal cells (MSCs) Membrane vesicles (MVs) Proliferation Differentiation Immunomodulation B lymphocytes |
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| Title | The Immunosuppressive Effect of Mesenchymal Stromal Cells on B Lymphocytes is Mediated by Membrane Vesicles |
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