Proteolytically degradable PEG hydrogel matrix mimicking tumor immune microenvironment for 3D co-culture of lung adenocarcinoma cells and macrophages

肿瘤微环境 免疫系统 基质(化学分析) 腺癌 PEG比率 细胞培养 化学 细胞生物学 癌症研究 免疫学 生物 医学 癌症 内科学 经济 遗传学 色谱法 财务
作者
Sora Lee,Chang Seok Ki
出处
期刊:Journal of Biomaterials Science-polymer Edition [Informa]
卷期号:34 (14): 1981-1999 被引量:2
标识
DOI:10.1080/09205063.2023.2204778
摘要

Tumor-associated macrophages and monocytes are the major stromal cell types found in the tumor immune microenvironment (TIME), which modulates tumor progression, invasion, and chemoresistance. To address the need for an in vitro three-dimensional tumor model for understanding the complex cellular interactions within the TIME, we propose a TIME-mimetic co-culture matrix composed of photo-crosslinked poly(ethylene glycol) hydrogels mimicking the characteristics of the tumor and stroma. Desmoplasia-mimetic microgels encapsulating lung adenocarcinoma cells (A549) were embedded with monocyte- or macrophage-type U937 cells in normal stroma-mimetic hydrogel, increasing the proximity between the two cell types. By modulating the proteolytic degradability of the hydrogels, we could separate different cell types with high purities for use in orthogonal assays. In addition, we demonstrated that U937 cells had distinct influences on A549 cell death depending on their activation states (i.e. monocyte, M0, or M1 phenotype). M1 macrophages suppressed tumor growth and increased the susceptibility of A549 cells to cisplatin. In contrast, monocytes upregulated cancer stem cell markers (OCT4, SOX2, and SHH) of A549 cells, showing M2-like features, such as downregulated expression of proinflammatory markers (IL6 and TNFα). These findings suggest that this co-culture system is potentially used for investigation of heterotypic cellular interactions in the TIME.The developed co-culture model successfully reproduces complex tumor immune microenvironment.The model is composed of tumor- and stroma-mimetic matrices containing tumor and immune cells.Sequential matrix degradation enabled the independent cell collection.
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