title: Monocyte/macrophage cytokine activity regulates vascular smooth muscle cell function within a degradable polyurethane scaffold.
abstract: Tissue engineering strategies rely on the ability to promote cell proliferation and migration into porous biomaterial constructs, as well as to support specific phenotypic states of the cells in vitro. The present study investigated the use of released factors from monocytes and their derived macrophages (MDM) and the mechanism by which they regulate vascular smooth muscle cell (VSMC) response in a VSMC-monocyte co-culture system within a porous degradable polyurethane (D-PHI) scaffold. VSMCs cultured in monocyte/MDM-conditioned medium (MCM), generated from the culture of monocytes/MDM on D-PHI scaffolds for up to 28 days, similarly affected VSMC contractile marker expression, growth and three-dimensional migration when compared to direct VSMC-monocyte co-culture. Monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) were identified as two cytokines present in MCM, at concentrations that have previously been shown to influence VSMC phenotype. VSMCs cultured alone on D-PHI scaffolds and exposed to MCP-1 (5 ng ml(-1)) or IL-6 (1 ng ml(-1)) for 7 days experienced a suppression in contractile marker expression (with MCP-1 or IL-6) and increased growth (with MCP-1) compared to no cytokine medium supplementation. These effects were also observed in VSMC-monocyte co-culture on D-PHI. Neutralization of IL-6, but not MCP-1, was subsequently shown to decrease VSMC growth and enhance calponin expression for VSMC-monocyte co-cultures on D-PHI scaffolds for 7 days, implying that IL-6 mediates VSMC response in monocyte-VSMC co-cultures. This study highlights the use of monocytes and their derived macrophages in conjunction with immunomodulatory biomaterials, such as D-PHI, as agents for regulating VSMC response, and demonstrates the importance of monocyte/MDM-released factors, such as IL-6 in particular, in this process.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: K G
authors.initials: KG
authors.lastname: Battiston
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Labow
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: Simmons
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada. Electronic address: paul.santerre@utoronto.ca.
authors.forename: J P
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D015153:Blotting, Western; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011140:Polyurethanes / Q000494:pharmacology*; D016062:Porosity; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D011140:Polyurethanes; D004247:DNA
keywords: Co-culture; Cytokines; Monocyte; Polyurethane; Smooth muscle cell