The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles

Manuela Budoni, Alessandra Fierabracci, Rosa Luciano, Stefania Petrini, Vincenzo Di Ciommo, Maurizio Muraca

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)369-379
Number of pages11
JournalCell Transplantation
Volume22
Issue number2
DOIs
Publication statusPublished - 2013

Fingerprint

Lymphocytes
Immunosuppressive Agents
Mesenchymal Stromal Cells
B-Lymphocytes
Membranes
Cell culture
Blood Cells
Blood
Cell Culture Techniques
Conveyors
T-cells
Flow cytometry
Confocal microscopy
Cell proliferation
Coculture Techniques
Confocal Microscopy
Natural Killer Cells
Dendritic Cells
Standardization
Cell Differentiation

Keywords

  • B lymphocytes
  • Differentiation
  • Immunomodulation
  • Membrane vesicles (MVs)
  • Mesenchymal stromal cells (MSCs)
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles. / Budoni, Manuela; Fierabracci, Alessandra; Luciano, Rosa; Petrini, Stefania; Di Ciommo, Vincenzo; Muraca, Maurizio.

In: Cell Transplantation, Vol. 22, No. 2, 2013, p. 369-379.

Research output: Contribution to journalArticle

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