三维模拟肝癌肿瘤微环境,可视化肝细胞、肝星状细胞和癌细胞之间的细胞间串扰

Q1 Engineering Smart Materials in Medicine Pub Date : 2023-01-01 DOI:10.1016/j.smaim.2022.12.002
Yaolin Liu , Xiaoqian Yang , Dong Jiang , Rongcheng Hu , Fangli Huang , Xuenong Zou , Chun Liu , Zhenwei Peng
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引用次数: 0

摘要

尽管大量研究集中于阐明肝细胞癌(HCC)微环境的功能机制,但肿瘤微环境中多个细胞之间的细胞间串扰仍不清楚。在这里,我们在仿生复合水凝胶中共同培养HCC细胞、肝星状细胞(HSC)和肝细胞的球体,以构建体外HCC微环境的3D模型。该模型在仿生3D微环境中再现了早期HCC的主要细胞成分,实现了细胞与微环境之间细胞相互作用的可视化。使用该模型,我们发现当与HCC细胞共培养时,HSC被激活,并释放胶原蛋白以重塑微环境,这反过来触发HCC细胞中更高的EMT水平。肝细胞也对HCC细胞的存在和共培养中HSC的激活作出反应,显示ALB、AFP和HNF4A的表达水平下调。该模型概括了HCC微环境中HSC的激活,并使多细胞相互作用的三维可视化,为研究HCC和相关肝纤维化的机制提供了一个仿生平台。
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3D biomimetic tumor microenvironment of HCC to visualize the intercellular crosstalk between hepatocytes, hepatic stellate cells, and cancer cells

While a significant number of studies have focused on elucidating the functioning mechanisms of the Hepatocellular carcinoma (HCC) microenvironment, the intercellular crosstalk between multiple cells in the tumor microenvironment remains unclear. Here we co-cultured spheroids of HCC cells, hepatic stellate cells (HSCs), and hepatocytes in a biomimetic composite hydrogel to construct a 3D model of the HCC microenvironment in vitro. The model reproduced the major cellular components of early HCC in a biomimetic 3D microenvironment, realizing the visualization of the cellular interplay between cells and the microenvironment. Using this model, we showed that the HSCs were activated when co-cultured with HCC cells and deposed collagen to remodel the microenvironment, which in turn triggered higher EMT levels in HCC cells. The hepatocytes also responded to the existence of HCC cells and the activation of HSCs in co-culture, showing the downregulated expression level of ALB, AFP, and HNF4A. This model recapitulated the activation of HSCs in the HCC microenvironment and enabled visualization of multicellular interplay in 3D, providing a biomimetic platform to investigate mechanisms of HCC and related hepatic fibrosis.

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来源期刊
Smart Materials in Medicine
Smart Materials in Medicine Engineering-Biomedical Engineering
CiteScore
14.00
自引率
0.00%
发文量
41
审稿时长
48 days
期刊最新文献
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