The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia: Evidence for an Involvement of Sphingosine-1-Phosphate Signalling

Giovanni Marfia, Stefania Elena Navone, Loubna Abdel Hadi, Moira Paroni, Valeria Berno, Matteo Beretta, Roberta Gualtierotti, Francesca Ingegnoli, Vincenzo Levi, Monica Miozzo, Jens Geginat, Lorenzo Fassina, Paolo Rampini, Carlo Tremolada, Laura Riboni, R. Campanella

Research output: Contribution to journalArticle

Abstract

Central nervous system (CNS) inflammation is primarily driven by microglial cells which secrete proinflammatory cytokines and undergo proliferation upon activation, as it occurs in neurodegenerative diseases. Uncontrolled or prolonged CNS inflammation is potentially harmful and can result in cellular damage. Recently, many studies have focused on human adipose tissue as an attractive source of cytokines with immunosuppressive properties that potentially modulate inflammation. Our study aimed to evaluate if different methods of human tissue collection could affect adipose mesenchymal stem cell (ADSC)-derived cytokine secretion and investigate the effects of ADSC secretome in modulating microglia activation and the possible implication of sphingosine-1-phosphate (S1P) in these effects. Our results demonstrate that the conditioned medium (CM) of ADSCs isolated by two different processing methods (lipoaspirate and Lipogems) significantly inhibited the lipopolysaccharide (LPS)-induced effects on microglia activation, including microglial expression of CD68, cytokine secretion, proliferation, and migration. Pulse studies with radiolabeled sphingosine demonstrated that LPS treatment of resting microglia induced a significant increase of both cellular and extracellular S1P. Moreover, and of relevance, FTY720, a functional antagonist of S1P receptor, inhibited the multiple LPS-induced proinflammatory effects on microglia, and S1P suppressed the anti-inflammatory effect of ADSC-CM. This suggests that LPS-mediated microglial activation is countered by ADSC-CM through the modulation of sphingosine kinase/S1P signalling.

Original languageEnglish
Pages (from-to)1095-1107
Number of pages13
JournalStem Cells and Development
Volume25
Issue number14
DOIs
Publication statusPublished - Jul 15 2016

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Microglia
Mesenchymal Stromal Cells
Lipopolysaccharides
Conditioned Culture Medium
Cytokines
Inflammation
Central Nervous System
Lysosphingolipid Receptors
Sphingosine
Immunosuppressive Agents
Neurodegenerative Diseases
Adipose Tissue
Anti-Inflammatory Agents
sphingosine 1-phosphate

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia : Evidence for an Involvement of Sphingosine-1-Phosphate Signalling. / Marfia, Giovanni; Navone, Stefania Elena; Hadi, Loubna Abdel; Paroni, Moira; Berno, Valeria; Beretta, Matteo; Gualtierotti, Roberta; Ingegnoli, Francesca; Levi, Vincenzo; Miozzo, Monica; Geginat, Jens; Fassina, Lorenzo; Rampini, Paolo; Tremolada, Carlo; Riboni, Laura; Campanella, R.

In: Stem Cells and Development, Vol. 25, No. 14, 15.07.2016, p. 1095-1107.

Research output: Contribution to journalArticle

Marfia, G, Navone, SE, Hadi, LA, Paroni, M, Berno, V, Beretta, M, Gualtierotti, R, Ingegnoli, F, Levi, V, Miozzo, M, Geginat, J, Fassina, L, Rampini, P, Tremolada, C, Riboni, L & Campanella, R 2016, 'The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia: Evidence for an Involvement of Sphingosine-1-Phosphate Signalling', Stem Cells and Development, vol. 25, no. 14, pp. 1095-1107. https://doi.org/10.1089/scd.2015.0268
Marfia, Giovanni ; Navone, Stefania Elena ; Hadi, Loubna Abdel ; Paroni, Moira ; Berno, Valeria ; Beretta, Matteo ; Gualtierotti, Roberta ; Ingegnoli, Francesca ; Levi, Vincenzo ; Miozzo, Monica ; Geginat, Jens ; Fassina, Lorenzo ; Rampini, Paolo ; Tremolada, Carlo ; Riboni, Laura ; Campanella, R. / The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia : Evidence for an Involvement of Sphingosine-1-Phosphate Signalling. In: Stem Cells and Development. 2016 ; Vol. 25, No. 14. pp. 1095-1107.
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