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构建复杂肠道类器官系统的技术进展与挑战

Technological advances and challenges in constructing complex gut organoid systems.

作者信息

Zheng Longjin, Zhan Yang, Wang Chenxuan, Fan Qigui, Sun Denglong, Li Yingmeng, Xiong Yanxia

机构信息

State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, China.

Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China.

出版信息

Front Cell Dev Biol. 2024 Aug 14;12:1432744. doi: 10.3389/fcell.2024.1432744. eCollection 2024.

DOI:10.3389/fcell.2024.1432744
PMID:39206092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349554/
Abstract

Recent advancements in organoid technology have heralded a transformative era in biomedical research, characterized by the emergence of gut organoids that replicate the structural and functional complexity of the human intestines. These stem cell-derived structures provide a dynamic platform for investigating intestinal physiology, disease pathogenesis, and therapeutic interventions. This model outperforms traditional two-dimensional cell cultures in replicating cell interactions and tissue dynamics. Gut organoids represent a significant leap towards personalized medicine. They provide a predictive model for human drug responses, thereby minimizing reliance on animal models and paving the path for more ethical and relevant research approaches. However, the transition from basic organoid models to more sophisticated, biomimetic systems that encapsulate the gut's multifaceted environment-including its interactions with microbial communities, immune cells, and neural networks-presents significant scientific challenges. This review concentrates on recent technological strides in overcoming these barriers, emphasizing innovative engineering approaches for integrating diverse cell types to replicate the gut's immune and neural components. It also explores the application of advanced fabrication techniques, such as 3D bioprinting and microfluidics, to construct organoids that more accurately replicate human tissue architecture. They provide insights into the intricate workings of the human gut, fostering the development of targeted, effective treatments. These advancements hold promise in revolutionizing disease modeling and drug discovery. Future research directions aim at refining these models further, making them more accessible and scalable for wider applications in scientific inquiry and clinical practice, thus heralding a new era of personalized and predictive medicine.

摘要

类器官技术的最新进展开创了生物医学研究的变革时代,其特点是出现了能够复制人类肠道结构和功能复杂性的肠道类器官。这些源自干细胞的结构为研究肠道生理学、疾病发病机制和治疗干预提供了一个动态平台。该模型在复制细胞相互作用和组织动态方面优于传统的二维细胞培养。肠道类器官代表了向个性化医学迈出的重要一步。它们为人类药物反应提供了一个预测模型,从而减少了对动物模型的依赖,并为更符合伦理和相关性更强的研究方法铺平了道路。然而,从基本的类器官模型过渡到更复杂的、模拟肠道多方面环境(包括其与微生物群落、免疫细胞和神经网络的相互作用)的仿生系统面临着重大的科学挑战。本综述集中探讨了克服这些障碍的最新技术进展,强调了整合不同细胞类型以复制肠道免疫和神经成分的创新工程方法。它还探讨了先进制造技术(如3D生物打印和微流体技术)在构建更准确复制人体组织结构的类器官方面的应用。它们为深入了解人类肠道的复杂运作提供了见解,促进了靶向、有效治疗方法的开发。这些进展有望彻底改变疾病建模和药物发现。未来的研究方向旨在进一步完善这些模型,使其更易于获取和扩展,以便在科学研究和临床实践中得到更广泛的应用,从而开创个性化和预测性医学的新时代。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8feb/11349554/e6e1e494b0e9/fcell-12-1432744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8feb/11349554/3195553a7f67/FCELL_fcell-2024-1432744_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8feb/11349554/e6e1e494b0e9/fcell-12-1432744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8feb/11349554/3195553a7f67/FCELL_fcell-2024-1432744_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8feb/11349554/e6e1e494b0e9/fcell-12-1432744-g001.jpg

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Bioact Mater. 2024 May 17;39:59-73. doi: 10.1016/j.bioactmat.2024.05.019. eCollection 2024 Sep.
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Human organoids-on-chips for biomedical research and applications.人源类器官芯片用于生物医学研究和应用。
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Listen to Your Gut: Key Concepts for Bioengineering Advanced Models of the Intestine.
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TGFB1 induces fetal reprogramming and enhances intestinal regeneration.TGFB1 诱导胎儿重编程并增强肠道再生。
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