Organoids are miniature tissue or organ models formed by stem cells (including pluripotent stem cells, tissue-specific adult stem cells, etc.) or progenitor cells in an in vitro three-dimensional culture system, which possess structural features and partial functions analogous to their corresponding in vivo organs. In 2009, the Hans Clevers laboratory developed the first intestinal organoid, marking the inception of organoid-based disease modeling. In 2011, both human pluripotent stem cells and primary adult stem cells were used to cultivate intestinal organoids; in the same year, retinal organoids derived from embryonic stem cells were generated. In 2012, retinal organoids derived from human pluripotent stem cells were successfully cultured. In 2013, research advances included the generation of brain, liver, kidney and pancreatic organoids from human pluripotent stem cells. In the subsequent years, prostate and lung organoids (2014), followed by mammary gland, fallopian tube and hippocampal organoids (2015), were successively developed. In 2020, researchers successfully cultivated snake venom gland organoids, and chondrosarcoma organoids were induced the following year. By 2022, hair and skin organoids were generated from human pluripotent stem cells, and by 2023, ventral thalamic organoids with nuclear characteristics of transcriptional diversity were derived from human embryonic stem cells (hESCs). To date, organoid models of the esophagus, retina, brain, kidney, liver, prostate, mammary gland and cornea have been successfully established, as well as organoid models of esophageal cancer and glioma.
The long development cycle and exorbitant cost of new drug research and development have severely hindered the drug development process. Organoids are characterized by higher clinical relevance, shorter experimental cycles and lower costs. With the evolution of regulatory frameworks, organoids and organ-on-a-chip models are poised to reshape the current landscape of new drug research and development.
In 2010, the U.S. Food and Drug Administration (FDA), in collaboration with the National Institutes of Health (NIH) and other institutions, launched the Tissue Chip Drug Screening Program. The initiative aimed to develop chips that mimic human organs, establish more accurate and effective drug screening models, reduce reliance on animal experiments in the drug research and development process, improve the success rate of drug development, and lower developmental costs and risks. The FDA Modernization Act 2.0 permits drug developers to use alternative methods, including organoids, for preclinical testing where appropriate, eliminating the mandatory requirement for animal experiments. This has paved the way and provided policy support for the application of organoids in drug research and development and other fields. The European Medicines Agency (EMA) issued the Guideline on the Regulatory Acceptance of the 3Rs (Replacement, Reduction, Refinement) Approaches, which established a submission pathway applicable for regulatory purposes and is also relevant to technologies such as organoids. In 2021, the Center for Drug Evaluation (CDE) of the National Medical Products Administration issued relevant guidelines encouraging the research and development of innovative biomimetic model technologies, including two-dimensional or three-dimensional tissue models and organoid models. In 2024, the CDE released the Guidelines for Model-Informed Drug Development for Rare Diseases (Draft for Comments), emphasizing that given the particularity of rare diseases, all available data should be fully explored and utilized. Sources of non-clinical research data include genetic, molecular, cellular, organoid, organ-on-a-chip and animal study data, which clearly defines the role of organoid data in the research and development of drugs for rare diseases.
In 2022, the clinical trial of the new drug SAR445088, a collaboration between Sanofi and organ-on-a-chip company Hesperos, was approved by the FDA. It became the world's first new drug to enter clinical trials based entirely on preclinical data obtained from organoid-on-a-chip research. In the same year, the clinical trial application for AVL-201, a product developed by Beijing Xunsheng Biomedical Research Co., Ltd. through an organoid high-throughput platform, was accepted. In 2023, MCLA-158, identified by Merus through screening a human organoid biobank, was approved for clinical trials by the FDA and is currently in Phase 2. In the same year, Hengrui Medicine's HRS-1893 tablets were approved to initiate clinical trials; IM83, a next-generation anti-tumor drug independently developed by Beijing ArtMia Cure Pharmaceutical Technology Co., Ltd., obtained IND approval based on organoid data; and QLF3108 for injection, a Class I novel anti-tumor bispecific antibody developed by Qilu Pharmaceutical, received clinical approval for the treatment of advanced solid tumors. In 2024, the clinical trial application for GC203, a gene-modified tumor-infiltrating lymphocyte (TIL) cell drug developed by JunSai Biotech via an organoid immune co-culture platform, was accepted.
Owing to their intrinsic characteristics, organoids play a pivotal role in drug screening, validation and optimization, bringing new opportunities and transformative changes to drug research and development. Meanwhile, organoids cultured from patients' own cells can be used to establish personalized disease models, which enable the testing of the efficacy of different drugs in individual patients and the formulation of personalized treatment regimens for them. Furthermore, organoids possess a certain capacity for self-organization and differentiation, which provides new insights for regenerative medicine research. With social development, the frequency and variety of infectious diseases are on the rise; organoids exhibit unique value in the research, prevention and control of acute infectious diseases, and can be used for the rapid screening of drugs for the treatment of such diseases. Despite their enormous potential, organoids currently face several challenges, such as the standardized culture of organoids, the complexity of the models, and ethical issues. The review was published online on March 17, 2026, in the Chinese Medical Journal . In summary, supported by relevant regulations, organoid models overcome the limitations of traditional drug testing models, accelerate drug testing processes, and improve the accuracy of preclinical safety and efficacy assessments, thereby reducing risks to patients and lowering drug development costs. Although technical and clinical challenges remain at present, with the advancement of relevant research, organoids hold tremendous potential in drug development, personalized therapy and other fields.
Reference
DOI: http://doi.org/10.1097/CM9.0000000000004067
About Dr. Yuzhu Zhang from Wenzhou Medical University
Dr. Zhang has long been engaged in research on breast cancer organoids and cancer stem cells, and possesses an in-depth understanding of the research progress and cutting-edge developments in this field. In the past five years, as first author he has published multiple SCI papers in journals including Molecular Therapy - Nucleic Acids, Cancer Letters, Cancer Cell International, and Breast Cancer Research and Treatment. His findings have been accepted by ASCO and published as abstracts in the Journal of Clinical Oncology.
