PMID- 27217090 OWN - NLM STAT- MEDLINE DCOM- 20170911 LR - 20181202 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 25 IP - 14 DP - 2016 Jul 15 TI - The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia: Evidence for an Involvement of Sphingosine-1-Phosphate Signalling. PG - 1095-107 LID - 10.1089/scd.2015.0268 [doi] AB - 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. FAU - Marfia, Giovanni AU - Marfia G AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Navone, Stefania Elena AU - Navone SE AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Hadi, Loubna Abdel AU - Hadi LA AD - 2 Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, University of Milan , Milan, Italy . FAU - Paroni, Moira AU - Paroni M AD - 3 Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy . FAU - Berno, Valeria AU - Berno V AD - 3 Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy . FAU - Beretta, Matteo AU - Beretta M AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Gualtierotti, Roberta AU - Gualtierotti R AD - 4 Division of Rheumatology, Istituto Gaetano Pini , Milano, Italy . FAU - Ingegnoli, Francesca AU - Ingegnoli F AD - 4 Division of Rheumatology, Istituto Gaetano Pini , Milano, Italy . FAU - Levi, Vincenzo AU - Levi V AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Miozzo, Monica AU - Miozzo M AD - 5 Division of Pathology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Geginat, Jens AU - Geginat J AD - 3 Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy . FAU - Fassina, Lorenzo AU - Fassina L AD - 6 Department of Health Sciences and Industrial and Information Engineering, University of Pavia , Pavia, Italy . FAU - Rampini, Paolo AU - Rampini P AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . FAU - Tremolada, Carlo AU - Tremolada C AD - 7 Istituto Image , Milan, Italy . FAU - Riboni, Laura AU - Riboni L AD - 2 Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, University of Milan , Milan, Italy . FAU - Campanella, Rolando AU - Campanella R AD - 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy . LA - eng PT - Journal Article DEP - 20160627 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Lysophospholipids) RN - 0 (Proteome) RN - 26993-30-6 (sphingosine 1-phosphate) RN - G926EC510T (Fingolimod Hydrochloride) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - Adipose Tissue/*cytology MH - Adult MH - Cell Proliferation/drug effects MH - Cell Separation MH - Chemotaxis/drug effects MH - Culture Media, Conditioned/pharmacology MH - Cytokines/metabolism MH - Down-Regulation/drug effects MH - Female MH - Fingolimod Hydrochloride/pharmacology MH - Humans MH - Inflammation/metabolism/*pathology MH - Lipopolysaccharides MH - Lysophospholipids/*metabolism MH - Male MH - Mesenchymal Stem Cells/cytology/drug effects/*metabolism MH - Microglia/metabolism/*pathology MH - Middle Aged MH - Phenotype MH - Proteome/*metabolism MH - *Signal Transduction/drug effects MH - Sphingosine/*analogs & derivatives/metabolism EDAT- 2016/05/25 06:00 MHDA- 2017/09/12 06:00 CRDT- 2016/05/25 06:00 PHST- 2016/05/25 06:00 [entrez] PHST- 2016/05/25 06:00 [pubmed] PHST- 2017/09/12 06:00 [medline] AID - 10.1089/scd.2015.0268 [doi] PST - ppublish SO - Stem Cells Dev. 2016 Jul 15;25(14):1095-107. doi: 10.1089/scd.2015.0268. Epub 2016 Jun 27.