Matrix-Bound Nanovesicles Recapitulate Extracellular Matrix Effects on Macrophage Phenotype
Matrix-Bound Nanovesicles Recapitulate Extracellular Matrix Effects on Macrophage Phenotype
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DOI：
10.1089/ten.tea.2017.0102
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发表时间：
2017-11-01
影响因子：
4.1
通讯作者：
Badylak, Stephen F.
中科院分区：
文献类型：
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作者：
Huleihel, Luai;Bartolacci, Joseph G.;Badylak, Stephen F.
早期巨噬细胞对生物材料的反应已被证明是下游结果的关键和预测性决定因素。当适当制备时，由哺乳动物细胞外基质（ECM）组成的生物支架已显示出促进巨噬细胞行为从促炎性表型向调节/抗炎性表型的转变，这又与结构性和功能性组织修复相关。然而，ECM生物支架促进这种表型转变的机制知之甚少。本研究表明，基质结合纳米囊泡（MBV），ECM生物支架的一个组成部分，是能够重演的ECM生物支架，它们来自巨噬细胞活化作用。发现从两种不同来源的组织（猪膀胱和小肠粘膜下层）分离的MBV富含miRNA 125 b-5 p、143- 3 p和145- 5 p。巨噬细胞内这些miRNA的抑制与基因和蛋白质表达谱相关，其与促炎表型而不是抗炎/调节表型更一致。MBV及其相关的miRNA货物似乎在介导ECM生物支架对巨噬细胞表型的影响中起重要作用。
The early macrophage response to biomaterials has been shown to be a critical and predictive determinant of downstream outcomes. When properly prepared, bioscaffolds composed of mammalian extracellular matrix (ECM) have been shown to promote a transition in macrophage behavior from a proinflammatory to a regulatory/anti-inflammatory phenotype, which in turn has been associated with constructive and functional tissue repair. The mechanism by which ECM bioscaffolds promote this phenotypic transition, however, is poorly understood. The present study shows that matrix-bound nanovesicles (MBV), a component of ECM bioscaffolds, are capable of recapitulating the macrophage activation effects of the ECM bioscaffold from which they are derived. MBV isolated from two different source tissues, porcine urinary bladder and small intestinal submucosa, were found to be enriched in miRNA125b-5p, 143-3p, and 145-5p. Inhibition of these miRNAs within macrophages was associated with a gene and protein expression profile more consistent with a proinflammatory rather than an anti-inflammatory/regulatory phenotype. MBV and their associated miRNA cargo appear to play a significant role in mediating the effects of ECM bioscaffolds on macrophage phenotype.