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首页> 外文期刊>Acta biomaterialia >Monocyte/macrophage cytokine activity regulates vascular smooth muscle cell function within a degradable polyurethane scaffold
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Monocyte/macrophage cytokine activity regulates vascular smooth muscle cell function within a degradable polyurethane scaffold

机译：单核细胞/巨噬细胞的细胞因子活性调节可降解聚氨酯支架内的血管平滑肌细胞功能

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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.
机译：组织工程策略依赖于促进细胞增殖和迁移到多孔生物材料结构中以及在体外支持细胞特定表型状态的能力。本研究调查了单核细胞及其衍生的巨噬细胞（MDM）中释放因子的使用以及它们在多孔可降解聚氨酯（D-）中的VSMC-单核细胞共培养系统中调节血管平滑肌细胞（VSMC）反应的机制。 PHI）支架。在单核细胞/ MDM条件培养基（MCM）中培养的VSMC由直接在D-PHI支架上培养单核细胞/ MDM长达28天产生，与直接VSMC相比，同样影响VSMC收缩标记的表达，生长和三维迁移-单核细胞共培养。单核细胞趋化蛋白1（MCP-1）和白细胞介素6（IL-6）被鉴定为MCM中存在的两种细胞因子，其浓度先前已显示出会影响VSMC表型。在D-PHI支架上单独培养并暴露于MCP-1（5 ng ml-1）或IL-6（1 ng ml-1）7天的VSMC经历了收缩标志物表达的抑制（使用MCP-1或IL- 6）与不添加细胞因子培养基相比，生长增加（使用MCP-1）。在D-PHI的VSMC-单核细胞共培养中也观察到了这些作用。随后显示，IL-6（而非MCP-1）的中和作用会降低VSMC生长，并增强D-PHI支架上VSMC-单核细胞共培养7天的钙蛋白表达，这暗示IL-6介导单核细胞中VSMC的应答。 VSMC共培养。这项研究着重介绍了将单核细胞及其衍生的巨噬细胞与免疫调节生物材料（例如D-PHI）一起用作调节VSMC反应的药物，并证明了单核细胞/ MDM释放因子（尤其是IL-6）的重要性，在这个过程中。

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