类器官疾病建模与干预策略开发——精准医学应用进展

doi:10.6040/j.issn.1671-7554.0.2026.1020

摘要/Abstract

摘要： 类器官是由原代组织来源细胞、多能干细胞或成体干细胞经体外培养形成的三维细胞培养物,通常由多种组织特异性细胞组成,具有自我更新、自组织及部分组织结构和功能特征。类器官能够在体外保留患者或疾病相关的遗传背景,并在细胞组成、组织结构、信号通路、代谢状态及多维组学特征等方面模拟疾病表型,因而可作为疾病模型构建、发病机制研究、药物筛选、安全性评价及个体化治疗反应预测的重要实验体系。随着培养体系、工程化技术和多组学分析方法的发展,类器官已不再局限于单一组织的形态模拟,逐渐发展为疾病建模、药物筛选、毒性评价、机制解析和个体化治疗预测功能的精准医学平台。本文围绕基于类器官的疾病建模与干预策略开发这一主题,归纳了类器官在疾病研究中的应用路径,重点介绍免疫化类器官、血管化类器官、神经与基质多细胞互作模型,以及微流控、器官芯片与多器官互作体系等复杂疾病类器官模型的构建进展,并结合代谢性肝病、慢性肾病及阿尔茨海默病等复杂疾病,探讨类器官模型在表型模拟、病理微环境重建和器官互作机制解析中的作用。此外,本文还梳理了3D生物打印、单细胞测序、空间转录组、人工智能辅助药物筛选和虚拟细胞等加速类器官应用的前沿交叉技术,并对成熟度、标准化程度、规模化提高及多模态数据整合等发展的重要方向进行展望。

关键词: 类器官, 精准医学, 疾病建模, 药物筛选与药效评价, 人工智能与虚拟细胞

Abstract: Organoids are three-dimensional cell culture systems generated in vitro from primary tissue-derived cells, pluripotent stem cells, or adult stem cells. They are typically composed of multiple tissue-specific cell types and exhibit self-renewal, self-organization, and selected structural and functional characteristics of native tissues. Organoids can retain patient- or disease-specific genetic backgrounds and recapitulate disease phenotypes in terms of cellular composition, tissue architecture, signaling pathways, metabolic states, and multidimensional omics features. They therefore provide valuable experimental platforms for disease modeling, mechanistic investigation, drug screening, safety assessment, and prediction of individualized therapeutic responses. With advances in culture systems, bioengineering technologies, and multi-omics analytical approaches, organoids are no longer limited to the morphological reconstruction of individual tissues. Instead, they are increasingly being developed into precision medicine platforms that integrate disease modeling, drug screening, toxicity evaluation, mechanistic analysis, and personalized treatment-response prediction. Focusing on organoid-based disease modeling and intervention strategy development, this review summarizes major applications of organoids in disease research, including immune-integrated organoids, vascularized organoids, multicellular models of neural-stromal interactions, as well as microfluidic systems, organ-on-chip platforms, and multi-organ interaction systems. Using complex diseases such as metabolic liver disease, chronic kidney disease, and Alzheimers disease as examples, we discuss the roles of organoid models in disease phenotype recapitulation, reconstruction of pathological microenvironments, and elucidation of inter-organ communication mechanisms. In addition, this review highlights emerging interdisciplinary technologies that are accelerating organoid research and application, including three-dimensional bioprinting, single-cell sequencing, spatial transcriptomics, artificial intelligence-assisted drug screening, and virtual cell modeling. Finally, key future directions are discussed, including improvements in organoid maturation, standardization, scalability, and multimodal data integration.

Key words: Organoids, Precision medicine, Disease modeling, Drug screening and efficacy evaluation, Artificial intelligence and virtual cells

中图分类号:

R329

范玉佳,吴贯召,耿文文,胡慧丽. 类器官疾病建模与干预策略开发——精准医学应用进展[J]. 山东大学学报 (医学版), 2026, 64(10): 95-103.

FAN Yujia, WU Guanzhao, GENG Wenwen, HU Huili. Organoid-based disease modeling and intervention strategy development: advances in precision medicine applications[J]. Journal of Shandong University (Health Sciences), 2026, 64(10): 95-103.

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