Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (10): 95-103.doi: 10.6040/j.issn.1671-7554.0.2026.1020

Previous Articles    

Organoid-based disease modeling and intervention strategy development: advances in precision medicine applications

FAN Yujia1, WU Guanzhao2, GENG Wenwen2, HU Huili1   

  1. 1. Department of Systems Biomedicine, School of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Central Laboratory, Qilu Hospital(Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266011, Shandong, China;
    3. Department of Breast Surgery, Qilu Hospital(Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266011, Shandong, China
  • Published:2026-10-10

PDF (PC)

3

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

CLC Number: 

  • R329
[1] Du H R, Guo L Q, Lian J B, et al. Establishment of epithelial inflammatory injury model using adult kidney organoids[J]. Life Med, 2024, 3(3): lnae022. DOI: 10.1093/lifemedi/lnae022
[2] Nan J, He X L, Liu X P, et al. Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes[J]. Nat Metab, 2026, 8(1): 139-158.
[3] Kiral F R, Cakir B, Tanaka Y, et al. Generation of ventralized human thalamic organoids with thalamic reticular nucleus[J]. Cell Stem Cell, 2023, 30(5): 677-688.
[4] Wang D, Zhang X, Tang X Y, et al. Generation of human nucleus basalis organoids with functional nbM-cortical cholinergic projections in transplanted assembloids[J]. Cell Stem Cell, 2025, 32(12): 1833-1848.
[5] Zeng P M, Sun X Y, Li Y, et al. Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids[J]. Stem Cell Reports, 2025, 20(9): 102601. DOI: 10.1016/j.stemcr.2025.102601
[6] 郭贝贝, 胡慧丽. 类器官在发育与再生中的研究进展[J]. 中国细胞生物学学报, 2021, 43(6): 1111-1119. Guo Beibei, Hu Huili. Research advances of organoids in development and regeneration[J]. Chinese Journal of Cell Biology, 2021, 43(6): 1111-1119.
[7] Zhao Y, Zhang B, Ma Y, et al. Distinct molecular profiles drive multifaceted characteristics of colorectal cancer metastatic seeds[J]. J Exp Med, 2024, 221(5): e20231359. DOI: 10.1084/jem.20231359
[8] Lin K, Deng X, Wang H, et al. Activation of ERBB4 pathway inhibits pathological transdifferentiation of lung epithelial progenitors into CD66c(+)basal cells in severe lung injury[J]. Adv Sci(Weinh), 2026, 13(37): e19151. DOI:10.1002/advs.202519151
[9] Hong F, Wang X D, Zhong N S, et al. The critical role of BMP signaling in gastric epithelial cell differentiation revealed by organoids[J]. Cell Regen, 2025, 14(1): 18. DOI: 10.1186/s13619-025-00237-x
[10] Hendriks D, Brouwers J F, Hamer K, et al. Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis[J]. Nat Biotechnol, 2023, 41(11): 1567-1581.
[11] Liu M, Zhang C, Gong X, et al. Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo[J]. Cell Stem Cell, 2024, 31(1): 52-70.
[12] Vishy C E, Thomas C, Vincent T, et al. Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease[J]. Cell Stem Cell, 2024, 31(4): 537-553.
[13] Guo L Q, Fan Y J, Sun H X, et al. Patient-derived kidney organoids recapitulate ADPKD and facilitate the identification of Rho pathway inhibitors as candidate therapeutics[J]. Cell Rep Med, 2026, 7(4): 102720. DOI:10.1016/j.xcrm.2025.101028
[14] Xu Z T, Yang H, Zhou Y R, et al. Whole-process 3D ECM-encapsulated organoid-based automated high-throughput screening platform accelerates drug discovery for rare diseases[J]. Life Med, 2025, 4(5): lnaf021. DOI: 10.1093/lifemedi/lnaf021
[15] Kaynak M, A?瘙塂ık M D, Inan E E, et al. Mechanotyping of organoids for assessing drug-induced injuries[J]. Adv Mater, 2026, 38(5): e09675. DOI:10.1002/adma.202509675
[16] Ji S, Feng L, Fu Z, et al. Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology[J]. Sci Transl Med, 2023, 15(706): eadg3358. DOI: 10.1126/scitranslmed.adg3358
[17] Wang S, Yang Y, Wang Y, et al. Mammary organoid-based depot for post-surgical chemotherapy and gland regeneration[J]. Nat Biomed Eng, 2026. DOI: 10.1038/s41551-026-01655-1
[18] Mao Y N, Hu H L. Establishment of advanced tumor organoids with emerging innovative technologies[J]. Cancer Lett, 2024, 598: 217122. DOI: 10.1016/j.canlet.2024.217122
[19] Ji L, Yan J, Losurdo N A, et al. Mutations in the spliceosomal gene SNW1 cause neurodevelopment disorders with microcephaly[J]. J Clin Investig, 2025, 135(18): 1-17.
[20] Pan Z, Yao Q, Kong W, et al. Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery[J]. Cell Stem Cell, 2025, 32(2): 227-245.
[21] Liu K S, Yan Z H, Bai D D, et al. Modeling post-gastrula development via bidirectional pluripotent stem cells[J]. Cell Res, 2025, 35(12): 954-969.
[22] Dekkers J F, Wiegerinck C L, de Jonge H R, et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids[J]. Nat Med, 2013, 19(7): 939-945.
[23] Ramalho A S, Furstova E, Vonk A M, et al. Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis[J]. Eur Respir J, 2021, 57(1): 1902426. DOI:10.1183/13993003.01902-2019
[24] Schwank G, Koo B K, Sasselli V, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients[J]. Cell Stem Cell, 2013, 13(6): 653-658.
[25] Geurts M H, de Poel E, Amatngalim G D, et al. CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank [J]. Cell Stem Cell, 2020, 26(4): 503-510.
[26] Qian Z P, Yang D, Li Y L, et al. Analysis of high glucose injury using human induced pluripotent stem cell-derived kidney organoids[J]. BMC Nephrol, 2026, 27(1): 53. DOI: 10.1186/s12882-025-04566-6
[27] Garreta E, Prado P, Stanifer M L, et al. A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells[J]. Cell Metab, 2022, 34(6): 857-873.
[28] Ouchi R, Togo S, Kimura M, et al. Modeling steatohe-patitis in humans with pluripotent stem cell-derived organoids[J]. Cell Metab, 2019, 30(2): 374-384.
[29] Digby J L M, Vanichapol T, Przepiorski A, et al. Eva-luation of cisplatin-induced injury in human kidney organoids[J]. Am J Physiol Ren Physiol, 2018, 315(2): 211-221.
[30] Lian J B, An Y C, Wei W J, et al. Transcriptional landscape and chromatin accessibility reveal key regulators for liver regenerative initiation and organoid formation[J]. Cell Rep, 2025, 44(5): 115633. DOI: 10.1016/j.celrep.2025.115633
[31] An Y C, Lian J B, Wei W J, et al. Activation and spatial redistribution of RNA splicing factors trigger hepatic regeneration[J]. Cell Mol Gastroenterol Hepatol, 2026, 20(2): 101654. DOI:10.1016/j.jcmgh.2025.101654
[32] Lin L, Pou Casellas C, Dost A F M, et al. Human airway submucosal gland organoids to study respiratory inflammation and infection[J]. Cell Stem Cell, 2025, 32(7): 1170-1182.
[33] Recaldin T, Steinacher L, Gjeta B, et al. Human organoids with an autologous tissue-resident immune compartment[J]. Nature, 2024, 633(8028): 165-173.
[34] De Crignis E, Hossain T, Romal S, et al. Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma[J]. Elife, 2021, 10: e68043. DOI: 10.7554/eLife.60747
[35] Wang Y, Lou R, Zhang Z, et al. Stromal BMP signaling regulates mucin production in the large intestine via interleukin-1/17[J]. Sci Adv, 2023, 9(31): eadd0699. DOI:10.1126/sciadv.adi1827
[36] Kim S Y, de Weert T A, Vermeulen M, et al. Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer[J]. Sci Adv, 2024, 10(12): eadk1234. DOI:10.1126/sciadv.adq1724
[37] Qin H L, Han Y, Li J Q, et al. piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer[J]. NPJ Precis Oncol, 2025, 9(1): 65. DOI:10.1038/s41698-025-00840-w
[38] Wang Q, Liu J, Yang M, et al. Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic the-rapy resistance in hepatocellular carcinoma[J]. Sig Transduct Target Ther, 2025, 10: 244. DOI:10.1038/s41392-025-02321-9
[39] 邱焕璐, 杜浩然, 胡慧丽. 类器官互作模型研究现状与趋势[J]. 中国细胞生物学学报, 2025, 47(9): 2259-2270. Qiu Huanlu, Du Haoran, Hu Huili. Research status and trends of organoid interaction models[J]. Chinese Journal of Cell Biology, 2025, 47(9): 2259-2270.
[40] Miao Y F, Pek N M, Tan C, et al. Co-development of mesoderm and endoderm enables organotypic vascula-rization in lung and gut organoids[J]. Cell, 2025, 188(16): 4295-4313.
[41] Chan B K C, Zhang C, Poon C H, et al. A combined enteric neuron-gastric tumor organoid reveals metabolic vulnerabilities in gastric cancer[J]. Cell Stem Cell, 2025, 32(10): 1595-1613.
[42] Childs C J, Poling H M, Chen K, et al. Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature[J]. Cell Stem Cell, 2025, 32(4): 640-651.
[43] Krueger D, Spoelstra W K, Mastebroek D J, et al. Epithelial tension controls intestinal cell extrusion[J]. Science, 2025, 389(6764): eadr8753. DOI:10.1126/science.adr8753
[44] 孟繁露, 韩益明, 修继冬, 等. 高通量自动化类器官芯片研究进展[J]. 天津医药, 2024, 52(1): 1-3. Meng Fanlu, Han Yiming, Xiu Jidong, et al. Advances in high-throughput automated organoid-on-a-chip system[J]. Tianjin Medical Journal, 2024, 52(1): 1-3.
[45] Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow[J]. Nat Biomed Eng, 2022, 6(4): 351-371.
[46] Lim J H, Mun S J, Kang H M, et al. Personalized pharmacokinetic-pharmacodynamic guided therapy via an induced pluripotent stem cell-derived multi-organoid platform in NF1-mutant breast cancer[J]. Sig Transduct Target Ther, 2026, 11: 79. DOI:10.1038/s41392-026-02595-7
[47] 杨柳, 陈泽宇, 姜德建. 类器官在药物评价中的应用[J]. 中南药学, 2026: 1-12. Yang Liu, Chen Zeyu, Jiang Dejian. Application of organoids in drug evaluation[J]. Central South Pharmacy, 2026: 1-12.
[48] Keshara R, Kuodyte K, Janosch A, et al. High-content screening of organoids reveals the mechanisms of human pancreas acinar specification[J]. Cell Stem Cell, 2026, 33(2): 325-339.
[49] Shinozawa T, Kimura M, Cai Y Q, et al. High-fidelity drug-induced liver injury screen using human pluripotent stem cell-derived organoids[J]. Gastroenterology, 2021, 160(3): 831-846.
[50] Ding S L, Hsu C, Wang Z H, et al. Patient-derived micro-organospheres enable clinical precision oncology[J]. Cell Stem Cell, 2022, 29(6): 905-917.
[51] Sun L, Zhang Y Y, Niu Y D, et al. Multi-lineage hepatic organoids reveal toxic exosome mediated indirect hepatotoxicity[J]. Nat Commun, 2026, 17: 2926. DOI:10.1038/s41467-026-69548-0
[52] El Abdellaoui Soussi F, Brusilovsky M, Buck E, et al. Autologous organoid-T cell co-culture platform for mode-ling of immune-mediated drug-induced liver injury[J]. Adv Sci, 2025, 12(43): e08584. DOI:10.1002/advs.202508584
[53] Gupta N, Zhang K, Sabbisetti V, et al. AAV for gene therapy drives a nephrotoxic response via NFkappaB in kidney organoids[J]. Signal Transduct Target Ther, 2025, 10(1): 252. DOI: 10.1038/s41392-025-02336-2
[54] Yuan X, Wu J Q, Sun Z, et al. Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure[J]. Cell Stem Cell, 2024, 31(4): 484-498.
[55] Skylar-Scott M A, Huang J Y, Lu A, et al. Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues[J]. Nat Biomed Eng, 2022, 6(4): 449-462.
[56] Roth J G, Brunel L G, Huang M S, et al. Spatially controlled construction of assembloids using bioprinting[J]. Nat Commun, 2023, 14: 4346. DOI:10.1038/s41467-023-40006-5
[57] Li C, Fleck J S, Martins-Costa C, et al. Single-cell brain organoid screening identifies developmental defects in autism[J]. Nature, 2023, 621: 46. DOI:10.1038/s41586-023-06473-y
[58] He Z, Maynard A, Jain A, et al. Lineage recording in human cerebral organoids[J]. Nature Methods, 2022, 19: 90-99. DOI: 10.1038/s41592-021-01344-8
[59] 尤晓宇, 林锴珺, 孙申飞, 等. 人工智能在类器官领域的机遇和应用进展[J]. 中国细胞生物学学报, 2025, 47(9): 2221-2232. You Xiaoyu, Lin Kaijun, Sun Shenfei, et al. Opportunities and application progress of artificial intelligence in the field of organoid[J]. Chinese Journal of Cell Biology, 2025, 47(9): 2221-2232.
[60] Tebon P J, Wang B, Markowitz A L, et al. Drug screening at single-organoid resolution via bioprinting and interferometry[J]. Nat Commun, 2023, 14(1): 3168. DOI: 10.1038/s41467-023-38832-8
[61] Zhang S, Li L, Yu P, et al. A deep learning model for drug screening and evaluation in bladder cancer organoids[J]. Front Oncol, 2023, 13: 1064548. DOI: 10.3389/fonc.2023.1064548
[62] Matthews J M, Schuster B, Kashaf S S, et al. Organo ID: a versatile deep learning platform for tracking and analysis of single-organoid dynamics[J]. PLoS Comput Biol, 2022, 18(11): e1010584. DOI:10.1371/journal.pcbi.1010584
[63] Bunne C, Roohani Y, Rosen Y, et al. How to build the virtual cell with artificial intelligence: priorities and opportunities[J]. Cell, 2024, 187(25): 7045-7063.
[1] YU Zhigang, ZHENG Chao. Current status, challenges and innovative approaches of multidisciplinary treatment for breast cancer [J]. Journal of Shandong University (Health Sciences), 2025, 63(1): 1-9.
[2] Andong GUO,Sentai DING. Progress in the establishment and application of organoids of bladder cancer [J]. Journal of Shandong University (Health Sciences), 2023, 61(11): 20-26.
[3] WANG Chuanxin. Liquid biopsy of tumor [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 64-71.
[4] YANG Jun. Medico-engineering cooperation: a strategic plateau of neurosurgery innovation and development in the era of precision medicine [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 83-88.
[5] WANG Linlin, SUN Yuping. From the perspective of clinicians: the application and reflection of artificial intelligence in cancer precision diagnosis and treatment [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 89-96.
[6] WANG Haitao. Development of precision medicine in the treatment of castration-resistant prostate cancer [J]. Journal of Shandong University (Health Sciences), 2019, 57(1): 30-35.
[7] WANG Hongyang. Development of tumor biomarkers in the age of precision medicine [J]. Journal of Shandong University (Health Sciences), 2018, 56(10): 1-2.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd