复杂肠道类器官系统构建中的技术进步与挑战
Technological advances and challenges in constructing complex gut organoid systems
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影响因子:4.3
分区:生物学2区 / 发育生物学2区 细胞生物学3区
发表日期:2024
作者:
Longjin Zheng, Yang Zhan, Chenxuan Wang, Qigui Fan, Denglong Sun, Yingmeng Li, Yanxia Xiong
DOI:
10.3389/fcell.2024.1432744
摘要
近年来，类器官技术的突破开启了生物医学研究的变革时代，特别是肠道类器官能够复制人类肠道的结构和功能复杂性。这些由干细胞衍生的结构为研究肠道生理、疾病发生机制及治疗干预提供了动态平台。该模型在复制细胞相互作用和组织动力学方面优于传统的二维细胞培养。肠道类器官代表了个性化医学的重要进步，为模拟人体药物反应提供了预测模型，减少了对动物模型的依赖，推动了更为伦理和相关的研究路径。然而，从基础类器官模型到更复杂的仿生系统的转变，涉及微生物群落、免疫细胞和神经网络等多方面环境的整合，面临重大科学挑战。本文重点介绍了近年来在克服这些障碍方面的技术进展，强调了创新工程方法在整合多种细胞类型以复制肠道免疫和神经组分中的应用。还探讨了先进制造技术（如3D生物打印和微流控）在构建更贴近人体组织结构的类器官中的应用。这些技术有助于深入理解人类肠道的复杂机制，促进靶向、有效的治疗策略的开发。这些进步有望革新疾病模型建立和药物发现。未来的研究方向包括进一步优化模型，使其更易获取和规模化，用于更广泛的科研和临床应用，开启个性化和预测性医学的新纪元。
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.