Shao Weidong, Xu Hui, Zeng Kanghua, Ye Mingzhou, Pei Renjun, Wang Kai
Organoid Innovation Center, Suzhou Institute of Nanotech and Nano-bionics, Chinese Academy of Sciences, 398 Ruoshui Rd, Suzhou, Jiangsu, 215123, China.
China Pharmaceutical University, 639 Longmian Rd, Nanjing, Jiangsu, 210009, China.
Stem Cell Res Ther. 2025 Jan 26;16(1):27. doi: 10.1186/s13287-025-04139-2.
The lack of in vivo accurate human liver models hinders the investigation of liver-related diseases, injuries, and drug-related toxicity, posing challenges for both basic research and clinical applications. Traditional cellular and animal models, while widely used, have significant limitations in replicating the liver's complex responses to various stressors. Liver organoids derived from human pluripotent stem cells, adult stem cells primary cells, or tissues can mimic diverse liver cell types, major physiological functions, and architectural features. Recent advancements in the field have shown that some liver organoids have sufficient accuracy to replicate specific aspects of the human liver's complexity. This review highlights recent progress in liver organoid research, with a particular emphasis on their potential for toxicity assessment and disease modeling. The intrinsic advantages of liver organoids include higher sensitivity and suitability for long-term studies, which enhance the predictive value in drug and nanomaterial toxicity testing. The integration of liver organoids with microfluidic devices enables the simulation of the liver microenvironment and facilitates high-throughput drug screening. The liver organoids also serve as ideal platforms for studying liver diseases such as hepatitis, liver fibrosis, viral liver diseases, and monogenic diseases. Additionally, this review discusses the advantages and limitations of liver organoids along with potential avenues for future research.
缺乏体内精确的人类肝脏模型阻碍了对肝脏相关疾病、损伤和药物相关毒性的研究，给基础研究和临床应用都带来了挑战。传统的细胞和动物模型虽然被广泛使用，但在复制肝脏对各种应激源的复杂反应方面存在重大局限性。源自人类多能干细胞、成体干细胞、原代细胞或组织的肝脏类器官可以模拟多种肝细胞类型、主要生理功能和结构特征。该领域的最新进展表明，一些肝脏类器官具有足够的准确性来复制人类肝脏复杂性的特定方面。本综述重点介绍了肝脏类器官研究的最新进展，特别强调了它们在毒性评估和疾病建模方面的潜力。肝脏类器官的固有优势包括更高的敏感性和适合长期研究，这提高了在药物和纳米材料毒性测试中的预测价值。将肝脏类器官与微流控装置相结合能够模拟肝脏微环境并促进高通量药物筛选。肝脏类器官也是研究肝炎、肝纤维化、病毒性肝病和单基因疾病等肝脏疾病的理想平台。此外，本综述还讨论了肝脏类器官的优势和局限性以及未来研究的潜在途径。
