Min Kiyoon, Karuppannan Sathish Kumar, Tae Giyoong
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
Biophys Rev (Melville). 2024 Jun 3;5(2):021306. doi: 10.1063/5.0197875. eCollection 2024 Jun.
Over the past few decades, extensive research has explored the development of supportive scaffold materials for hepatic cell culture, to effectively mimic microenvironments. It is crucial for hepatic disease modeling, drug screening, and therapeutic evaluations, considering the ethical concerns and practical challenges associated with experiments. This review offers a comprehensive perspective on hepatic cell culture using bioscaffolds by encompassing all stages of hepatic diseases-from a healthy liver to fibrosis and hepatocellular carcinoma (HCC)-with a specific focus on matrix stiffness. This review begins by providing physiological and functional overviews of the liver. Subsequently, it explores hepatic cellular behaviors dependent on matrix stiffness from previous reports. For hepatic cell activities, softer matrices showed significant advantages over stiffer ones in terms of cell proliferation, migration, and hepatic functions. Conversely, stiffer matrices induced myofibroblastic activation of hepatic stellate cells, contributing to the further progression of fibrosis. Elevated matrix stiffness also correlates with HCC by increasing proliferation, epithelial-mesenchymal transition, metastasis, and drug resistance of HCC cells. In addition, we provide quantitative information on available data to offer valuable perspectives for refining the preparation and development of matrices for hepatic tissue engineering. We also suggest directions for further research on this topic.
在过去几十年里，广泛的研究探索了用于肝细胞培养的支持性支架材料的开发，以有效模拟微环境。考虑到与实验相关的伦理问题和实际挑战，这对于肝病建模、药物筛选和治疗评估至关重要。本综述通过涵盖肝病的各个阶段——从健康肝脏到纤维化和肝细胞癌（HCC）——对使用生物支架进行肝细胞培养提供了全面的视角，特别关注基质硬度。本综述首先对肝脏进行生理和功能概述。随后，它从先前的报告中探讨了依赖于基质硬度的肝细胞行为。对于肝细胞活动，在细胞增殖、迁移和肝功能方面，较软的基质比较硬的基质显示出显著优势。相反，较硬的基质诱导肝星状细胞的肌成纤维细胞活化，促进纤维化的进一步发展。基质硬度升高还通过增加肝癌细胞的增殖、上皮-间质转化、转移和耐药性与肝癌相关。此外，我们提供现有数据的定量信息，为改进肝组织工程基质的制备和开发提供有价值的观点。我们还提出了关于该主题进一步研究的方向。
