Yaolin Liu , Xiaoqian Yang , Dong Jiang , Rongcheng Hu , Fangli Huang , Xuenong Zou , Chun Liu , Zhenwei Peng
{"title":"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","authors":"Yaolin Liu , Xiaoqian Yang , Dong Jiang , Rongcheng Hu , Fangli Huang , Xuenong Zou , Chun Liu , Zhenwei Peng","doi":"10.1016/j.smaim.2022.12.002","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>in vitro</em>. 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.</p></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"4 ","pages":"Pages 384-395"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"3D biomimetic tumor microenvironment of HCC to visualize the intercellular crosstalk between hepatocytes, hepatic stellate cells, and cancer cells\",\"authors\":\"Yaolin Liu , Xiaoqian Yang , Dong Jiang , Rongcheng Hu , Fangli Huang , Xuenong Zou , Chun Liu , Zhenwei Peng\",\"doi\":\"10.1016/j.smaim.2022.12.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <em>in vitro</em>. 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.</p></div>\",\"PeriodicalId\":22019,\"journal\":{\"name\":\"Smart Materials in Medicine\",\"volume\":\"4 \",\"pages\":\"Pages 384-395\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Smart Materials in Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590183422000618\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Engineering\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Smart Materials in Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590183422000618","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Engineering","Score":null,"Total":0}
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.