重塑细胞间互动：类器官共培养模型赋能疾病机制与治疗探索

doi:10.12300/j.issn.1674-5817.2024.164

实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (3): 309-317.DOI: 10.12300/j.issn.1674-5817.2024.164

重塑细胞间互动：类器官共培养模型赋能疾病机制与治疗探索

谭邓旭¹^,²(), 马一凡¹, 刘可¹, 张延英¹()(), 师长宏²()()

^1.甘肃中医药大学第一临床医学院, 兰州 730030
^2.空军军医大学实验动物中心, 西安 710032

收稿日期:2024-11-07 修回日期:2025-02-06 出版日期:2025-07-07 发布日期:2025-06-25
通讯作者: 师长宏（1973—），男，博士，教授，研究方向：肿瘤模型制备及评价。E-mail： changhong@fmmu.edu.cn。ORCID：0000-0001-7490-3593；
张延英（1964—），男，硕士，教授，研究方向：实验动物学。E-mail：1360599656@qq.com。ORCID：0000-0002-2097-9207
作者简介:谭邓旭（1991—），男，硕士研究生，研究方向：类器官模型制备及应用。E-mail： 494117685@qq.com。ORCID：0000-0002-3685-9103
基金资助:
陕西省创新能力支撑计划项目“靶向MAOA促进胰腺癌免疫治疗”(2024CX-GXPT-41);甘肃省中医药研究中心开放课题“人源化PDX模型在胰腺癌免疫治疗研究的应用”(zyzx-2020-zx22);甘肃中医药大学研究生创新项目“肿瘤类器官与人免疫细胞共培养模型的建立及应用”

Reshaping Intercellular Interactions: Empowering the Exploration of Disease Mechanisms and Therapies Using Organoid Co-Culture Models

TAN Dengxu¹^,²(), MA Yifan¹, LIU Ke¹, ZHANG Yanying¹()(), SHI Changhong²()()

^1.First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou 730030, China
^2.Laboratory Animal Center, Fourth Military Medical University, Xi'an 710032, China

Received:2024-11-07 Revised:2025-02-06 Published:2025-06-25 Online:2025-07-07
Contact: SHI Changhong (ORCID: 0000-0001-7490-3593), E-mail: changhong@fmmu.edu.cn;
ZHANG Yanying (ORCID: 0000-0002-2097-9207), E-mail: 1360599656@qq.com

摘要/Abstract

摘要：

类器官共培养模型（organoid co-culture model）作为一种重现三维微环境以研究细胞间相互作用的新型工具，近年来在生物医学研究中展现了显著的应用潜力。该模型通过模拟体内组织的微环境，能够为研究细胞间复杂互动提供更为精准的实验平台，尤其在肿瘤免疫逃逸机制、药物敏感性测试、神经退行性疾病的病理特征揭示等方面具有重要价值。然而，类器官共培养模型在标准化操作、规模化培养、伦理规范和未来发展方向等方面仍面临诸多挑战，特别是在实验动物学领域，如何有效地将类器官与传统实验动物模型相结合，以及如何在不同研究需求中选择合适的模型并探索其替代潜能，仍是当前亟待解决的问题。在伦理审批和动物实验替代方面，类器官共培养模型提供了一种更加符合“替代、减少、优化（replacement，reduction，refinement，3R）”原则的实验方案，可能成为替代传统实验动物模型的重要工具。为此，本文回顾了该领域的最新进展与面临的关键挑战，详细描述了类器官共培养模型的构建方法，并阐述了其在发病机制研究和药物筛选中的应用。文章还系统比较了类器官共培养模型与传统实验动物模型的差异，探讨了二者在具体应用场景中的选择依据。此外，本文讨论了类器官共培养模型在实验动物替代中的潜在价值，并展望了该技术未来的发展趋势。通过这些讨论，本文旨在推动类器官共培养技术的创新与发展，并为未来相关研究提供新的视角和科学依据。

关键词: 细胞间互动, 类器官, 共培养, 实验动物

Abstract:

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

Key words: Intercellular interactions, Organoids, Co-culture, Laboratory animals

中图分类号:

R-332

谭邓旭,马一凡,刘可,等. 重塑细胞间互动：类器官共培养模型赋能疾病机制与治疗探索[J]. 实验动物与比较医学, 2025, 45(3): 309-317. DOI: 10.12300/j.issn.1674-5817.2024.164.

TAN Dengxu,MA Yifan,LIU Ke,et al. Reshaping Intercellular Interactions: Empowering the Exploration of Disease Mechanisms and Therapies Using Organoid Co-Culture Models[J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 309-317. DOI: 10.12300/j.issn.1674-5817.2024.164.

图/表 3

参考文献 40

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比较维度 Comparison dimension	类器官共培养模型 Organoid co-culture model	实验动物模型 Laboratory animal model
复杂性 Complexity	低：可控的细胞组成和环境	高：系统的生物复杂性
伦理问题 Ethical issues	较少：不涉及活体动物	较多：动物实验伦理问题
时间成本 Time cost	较短：快速获取结果	较长：动物的生长与繁殖
生理相关性 Physiological relevance	较低：缺乏全身系统	高：能反映全身生理状态
研究范围 Scope of research	细胞和局部微环境的研究	全身生理和行为的研究
疾病建模 Disease modeling	对人类特异性疾病建模具有高度准确性	受物种差异限制
药物测试 Drug testing	精确测试人类特异性的药物反应；高通量	全身药代动力学数据

比较维度 Comparison dimension	类器官共培养模型 Organoid co-culture model	实验动物模型 Laboratory animal model
复杂性 Complexity	低：可控的细胞组成和环境	高：系统的生物复杂性
伦理问题 Ethical issues	较少：不涉及活体动物	较多：动物实验伦理问题
时间成本 Time cost	较短：快速获取结果	较长：动物的生长与繁殖
生理相关性 Physiological relevance	较低：缺乏全身系统	高：能反映全身生理状态
研究范围 Scope of research	细胞和局部微环境的研究	全身生理和行为的研究
疾病建模 Disease modeling	对人类特异性疾病建模具有高度准确性	受物种差异限制
药物测试 Drug testing	精确测试人类特异性的药物反应；高通量	全身药代动力学数据

重塑细胞间互动：类器官共培养模型赋能疾病机制与治疗探索

Reshaping Intercellular Interactions: Empowering the Exploration of Disease Mechanisms and Therapies Using Organoid Co-Culture Models

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