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肝脏类器官:肝脏学的当前进展与未来应用

Liver organoids: Current advances and future applications for hepatology.

作者信息

Kim Yohan, Kang Minseok, Mamo Michael Girma, Adisasmita Michael, Huch Meritxell, Choi Dongho

机构信息

Department of MetaBioHealth, Sungkyunkwan University, Suwon, Korea.

Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Korea.

出版信息

Clin Mol Hepatol. 2025 Feb;31(Suppl):S327-S348. doi: 10.3350/cmh.2024.1040. Epub 2024 Dec 26.

Abstract

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.

摘要

自组织肝类器官的创建代表了朝着解决同种异体肝移植中持续存在的器官短缺危机迈出的重要一步,尽管这一步还比较小。然而,研究人员已经认识到,实现一个功能完全正常的完整肝脏仍然是一个遥远的目标,基于类器官的肝脏生成的最初抱负已暂时搁置。相反,肝类器官彻底改变了肝病学领域,将其影响力扩展到精准医学和分子医学的各个领域。这些三维培养物能够复制人类肝功能和病理的关键特征,为人类相关疾病建模、CRISPR基因编辑以及动物模型无法完成的高通量药物筛选开辟了新途径。此外,在创建更复杂系统方面的进展导致了多细胞组装体、动态芯片类器官系统和三维生物打印技术的发展。这些创新能够对肝脏微环境和复杂的组织相互作用进行详细建模。再生医学和移植应用方面的进展不断发展,并努力克服生物相容性和致瘤性方面的障碍。在这篇综述中,我们通过深入了解该领域目前的状况以及塑造其未来的关键进展,来审视肝类器官研究的现状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11925438/9968dd5bd9a6/cmh-2024-1040f1.jpg

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