细胞外基质
基质金属蛋白酶
自愈水凝胶
细胞生物学
巨噬细胞极化
基质(化学分析)
下调和上调
MMP9公司
巨噬细胞
材料科学
乙二醇
肿瘤坏死因子α
细胞培养
三维细胞培养
生物物理学
化学
免疫学
生物
细胞
生物化学
体外
复合材料
高分子化学
遗传学
有机化学
基因
作者
Minchae Kim,Sora Lee,Chang Seok Ki
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2019-01-04
卷期号:5 (2): 922-932
被引量:24
标识
DOI:10.1021/acsbiomaterials.8b01150
摘要
Although macrophages undergo dynamic cellular responses in diverse extracellular environments, macrophage research has mostly relied on conventional culture methodologies such as two-dimensional and suspension cultures. In contrast, recent efforts have revealed evidence of the characteristic cellular behaviors of macrophages in actual tissues using a three-dimensional (3D) culture matrix. In this work, we exploited a poly(ethylene glycol)-based hydrogel as a macrophage culture matrix and observed cellular behaviors in 3D by manipulating the matrix properties. In the 3D microenvironment, macrophage-like RAW264.7 cells proliferated and formed spherical clusters by degrading the surrounding hydrogel network. Interestingly, we observed the significant upregulation of matrix metalloproteinases (MMPs) (i.e., MMP9 and MMP14) as well as M1 polarization markers (i.e., iNOS, COX2, TNF-α) in 3D, whereas M2 polarization markers (i.e., CD206, Arg1, TGF-β) were downregulated. Specifically, the expressions of both M1 and M2 markers were simultaneously increased in a stiff matrix compared to those of a soft matrix. In addition, matrix degradability significantly influenced the TNF-α secretion of encapsulated RAW264.7 cells. The MMP sensitivity of the hydrogel decreased TNF-α expression in a soft matrix, whereas it upregulated TNF-α in a stiff matrix compared to those of MMP-insensitive hydrogel. These findings suggest that the highly tunable poly(ethylene glycol) hydrogels can dictate macrophage behavior by altering the surrounding 3D microenvironment.
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