title: Topographical cues regulate the crosstalk between MSCs and macrophages.
abstract: Implantation of scaffolds may elicit a host foreign body response triggered by monocyte/macrophage lineage cells. Growing evidence suggests that topographical cues of scaffolds play an important role in MSC functionality. In this work, we examined whether surface topographical features can regulate paracrine interactions that MSCs establish with macrophages. Three-dimensional (3D) topography sensing drives MSCs into a spatial arrangement that stimulates the production of the anti-inflammatory proteins PGE2 and TSG-6. Compared to two-dimensional (2D) settings, 3D arrangement of MSCs co-cultured with macrophages leads to an important decrease in the secretion of soluble factors related with inflammation and chemotaxis including IL-6 and MCP-1. Attenuation of MCP-1 secretion in 3D co-cultures correlates with a decrease in the accumulation of its mRNA levels in MSCs and macrophages. Using neutralizing antibodies, we identified that the interplay between PGE2, IL-6, TSG-6 and MCP-1 in the co-cultures is strongly influenced by the micro-architecture that supports MSCs. Local inflammatory milieu provided by 3D-arranged MSCs in co-cultures induces a decrease in monocyte migration as compared to monolayer cells. This effect is partially mediated by reduced levels of IL-6 and MCP-1, proteins that up-regulate each other's secretion. Our findings highlight the importance of topographical cues in the soluble factor-guided communication between MSCs and macrophages.
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Vallés
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Bensiamar
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Crespo
authors.affiliation: Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain; Departamento de Ingenieria Química, Instituto de Nanociencia de Aragón (INA), Edificio I+D, Universidad de Zaragoza, C/Mariano Esquillor, 50018 Zaragoza, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arruebo
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilaboa
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain. Electronic address: laura.saldana@salud.madrid.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Saldaña
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D015232:Dinoprostone
keywords: Immunomodulation; Macrophage; Mesenchymal stem cell; Porosity; Surface topography