Huang Dantong, Gibeley Sarah B, Xu Cong, Xiao Yang, Celik Ozgenur, Ginsberg Henry N, Leong Kam W
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY 10032, USA.
Adv Funct Mater. 2020 Oct 28;30(44). doi: 10.1002/adfm.201909553. Epub 2020 Feb 19.
The burden of liver diseases is increasing worldwide, accounting for two million deaths annually. In the past decade, tremendous progress has been made in the basic and translational research of liver tissue engineering. Liver microtissues are small, three-dimensional hepatocyte cultures that recapitulate liver physiology and have been used in biomedical research and regenerative medicine. This review summarizes recent advances, challenges, and future directions in liver microtissue research. Cellular engineering approaches are used to sustain primary hepatocytes or produce hepatocytes derived from pluripotent stem cells and other adult tissues. Three-dimensional microtissues are generated by scaffold-free assembly or scaffold-assisted methods such as macroencapsulation, droplet microfluidics, and bioprinting. Optimization of the hepatic microenvironment entails incorporating the appropriate cell composition for enhanced cell-cell interactions and niche-specific signals, and creating scaffolds with desired chemical, mechanical and physical properties. Perfusion-based culture systems such as bioreactors and microfluidic systems are used to achieve efficient exchange of nutrients and soluble factors. Taken together, systematic optimization of liver microtissues is a multidisciplinary effort focused on creating liver cultures and on-chip models with greater structural complexity and physiological relevance for use in liver disease research, therapeutic development, and regenerative medicine.
肝脏疾病的负担在全球范围内不断增加，每年导致200万人死亡。在过去十年中，肝脏组织工程的基础研究和转化研究取得了巨大进展。肝脏微组织是小型三维肝细胞培养物，可重现肝脏生理功能，已用于生物医学研究和再生医学。本文综述了肝脏微组织研究的最新进展、挑战和未来方向。细胞工程方法用于维持原代肝细胞或产生源自多能干细胞和其他成年组织的肝细胞。三维微组织通过无支架组装或支架辅助方法（如大封装、液滴微流控和生物打印）生成。肝脏微环境的优化需要纳入合适的细胞组成以增强细胞间相互作用和特定微环境信号，并创建具有所需化学、机械和物理特性的支架。基于灌注的培养系统（如生物反应器和微流控系统）用于实现营养物质和可溶性因子的有效交换。总之，肝脏微组织的系统优化是一项多学科努力，专注于创建具有更高结构复杂性和生理相关性的肝脏培养物和芯片模型，用于肝脏疾病研究、治疗开发和再生医学。
