title: Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles.
abstract: Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise macrophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of ​lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms.
authors.affiliation: Stem Cell Biology and Regenerative Medicine Group, Reading School of Pharmacy, University of Reading, Whiteknights Campus, PO Box 226, Reading, RG6 6AP, UK. m.zeuner@pgr.reading.ac.uk.
authors.forename: Marie-Theres
authors.initials: MT
authors.lastname: Zeuner
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights Campus, Reading, UK. ketan.patel@reading.ac.uk.|Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Albertstr. 19, 79104, Freiburg, Germany. ketan.patel@reading.ac.uk.
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
authors.affiliation: Interdisciplinary Center for Clinical Research Aachen (IZKF Aachen), RWTH Aachen University, Aachen, Germany. Bernd.Denecke@rwth-aachen.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Denecke
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Bernd.Giebel@uk-essen.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Giebel
authors.affiliation: Stem Cell Biology and Regenerative Medicine Group, Reading School of Pharmacy, University of Reading, Whiteknights Campus, PO Box 226, Reading, RG6 6AP, UK. d.widera@reading.ac.uk.
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
mesh_terms: D016764:Cell Polarity / Q000187:drug effects; D000067128:Extracellular Vesicles / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4
references.citation: Nat Immunol. 2008 Apr;9(4):361-8
references.pmid: 18297073
references.citation: Stem Cell Rev. 2013 Feb;9(1):32-43
references.pmid: 22529014
references.citation: Int J Cancer. 1980 Aug;26(2):171-6
references.pmid: 6970727
references.citation: Stem Cell Res Ther. 2015;6:75
references.pmid: 25890074
references.citation: Mol Biol Cell. 2002 Dec;13(12):4279-95
references.pmid: 12475952
references.citation: Stem Cell Res. 2010 May;4(3):214-22
references.pmid: 20138817
references.citation: Nat Immunol. 2014 Nov;15(11):1009-16
references.pmid: 25329189
references.citation: J Cell Biol. 2013 Feb 18;200(4):373-83
references.pmid: 23420871
references.citation: Science. 2007 Mar 16;315(5818):1576-9
references.pmid: 17322030
references.citation: Mediators Inflamm. 2010;2010. pii: 672395. doi: 10.1155/2010/672395
references.pmid: 20706656
references.citation: J Extracell Vesicles. 2015 May 14;4:27066
references.pmid: 25979354
references.citation: PLoS One. 2013;8(2):e56709
references.pmid: 23437218
references.citation: Nat Med. 2005 Apr;11(4):367-8
references.pmid: 15812508
references.citation: J Immunol. 1981 Jul;127(1):288-93
references.pmid: 7240745
references.citation: Stem Cell Rev. 2015 Aug;11(4):621-34
references.pmid: 25865145
references.citation: FASEB J. 2014 Sep;28(9):3856-66
references.pmid: 24830384
references.citation: Stem Cells Transl Med. 2015 Oct;4(10):1131-43
references.pmid: 26339036
references.citation: Blood. 2012 Jan 19;119(3):756-66
references.pmid: 22031862
references.citation: Cell Stem Cell. 2009 Jul 2;5(1):54-63
references.pmid: 19570514
references.citation: J Transl Med. 2015;13:308
references.pmid: 26386558
references.citation: Leukemia. 2013 Feb;27(2):500-3
references.pmid: 22878604
references.citation: J Invest Dermatol. 2006 Oct;126(10):2323-31
references.pmid: 16874314
references.citation: Stem Cells. 2008 Jan;26(1):279-89
references.pmid: 17962701
references.citation: Leukemia. 2014 Apr;28(4):970-3
references.pmid: 24445866
references.citation: Int J Biochem Cell Biol. 2012 Jan;44(1):11-5
references.pmid: 22024155
references.citation: Stem Cell Res. 2007 Nov;1(2):129-37
references.pmid: 19383393
references.citation: Cytotechnology. 2015 Oct;67(5):793-807
references.pmid: 24798808
references.citation: J Immunol. 2001 Nov 15;167(10):5887-94
references.pmid: 11698465
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
references.pmid: 11095740
references.citation: Transfusion. 2014 May;54(5):1418-37
references.pmid: 24898458
references.citation: FASEB J. 2006 Apr;20(6):661-9
references.pmid: 16581974
references.citation: J Am Soc Nephrol. 2009 May;20(5):1053-67
references.pmid: 19389847
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Feb;288(2):R345-53
references.pmid: 15637171
references.citation: Cell. 2011 Nov 11;147(4):868-80
references.pmid: 22078883
references.citation: J Extracell Vesicles. 2015 Dec 31;4:30087
references.pmid: 26725829
references.citation: Stem Cells. 2006 Dec;24(12):2744-52
references.pmid: 16902195
references.citation: Int Immunopharmacol. 2014 Nov;23(1):37-45
references.pmid: 25130606
references.citation: PLoS One. 2010;5(4):e10088
references.pmid: 20436665
references.citation: Trends Immunol. 2002 Mar;23(3):135-9
references.pmid: 11864841