Organoids in biomedicine: Bridging innovation, disease modeling, and regulatory transformation

Abstract

Organoids, which are three-dimensional cultures derived from pluripotent or adult stem cells, meticulously mimic human organ architecture and function, revolutionizing biomedical research. Patient-derived organoids have emerged as powerful tools in disease modeling, particularly in cancer research. For instance, in the case of colorectal cancer, organoids are developed from tumor tissues of patients, allowing for drug sensitivity tests that can inform personalized treatment plans, as seen in the case of a patient responding well to specific chemotherapy drugs. In addition, organoids have been used to study regenerative mechanisms, such as the repair of intestinal stem cells post-radiation, showcasing their versatility in biomedical research. In drug development, they facilitate screening for efficacy and toxicity, with applications in testing poly-ADP ribose polymerase (PARP) inhibitors and cosmetic ingredients, while aligning with ethical imperatives as the U.S. Food and Drug Administration (FDA) plans to phase out animal testing for certain drugs by 2025. In addition, organoids show promise in regenerative medicine, such as endometrial and retinal regeneration, and bone tissue engineering. Despite challenges such as variable culture conditions, limited vascularization, and high costs, standardizing protocols and integrating microenvironmental factors will enhance their clinical utility, driving a shift toward human-centric therapeutic advancements.

The rapid evolution of stem cell and organoid technologies has revolutionized biomedical research, offering unprecedented opportunities to model human development, disease mechanisms, and therapeutic interventions ¹ . This special issue of Cell Transplantation, “Stem Cells and Organoids,” highlights cutting-edge advancements in stem cell biology and organoid systems, underscoring their transformative potential in both basic science and clinical translation. Notably, recent regulatory shifts, such as the US Food and Drug Administration’s (FDA) 2025 plan to phase out animal testing for monoclonal antibodies and other drugs, further emphasize the urgency of adopting human-relevant models like organoids. These innovations not only align with ethical imperatives but also promise to enhance drug safety, reduce costs, and accelerate therapeutic discovery.

Organoids: a paradigm shift in biomedical research

Organoids, which are three-dimensional cultures derived from pluripotent or adult stem cells, accurately mimic the architecture and function of human organs. Their applications span regenerative medicine, disease modeling, drug screening, and toxicology testing. For instance, patient-derived organoids (PDOs) have emerged as powerful tools for personalized medicine, enabling researchers to replicate genetic profiles and test drug responses in vitro. A study by Chang et al. ² demonstrated that ovarian cancer PDOs faithfully captured tumor histology, mutation profiles, and drug sensitivity, highlighting their utility in predicting patient-specific therapeutic outcomes. Similarly, Li et al. ³ emphasized the role of colorectal cancer PDOs in guiding chemotherapy and targeted therapy decisions, reducing adverse effects and resistance.

Organoids in disease modeling and drug development

Organoid technology has unlocked new avenues for studying complex diseases, from developmental disorders to cancer ¹ . For example, Guan et al. ⁴ explored the role of interleukin-33 (IL-33) in intestinal stem cell regeneration after radiation injury using organoid cultures. Recent studies have highlighted that IL-33 enhances transforming growth factor-β (TGF-β) signaling to facilitate epithelial repair, a mechanism that is pivotal in the progression of gastrointestinal cancers and offers potential therapeutic targets for such conditions. In cancer research, Cao et al. ⁵ utilized ovarian cancer organoids to investigate poly-ADP ribose polymerase (PARP) inhibitor resistance, identifying early apoptosis and DNA repair pathways as key mechanisms. Such models provide a platform to dissect disease pathways and evaluate novel therapies in a human-specific context.

The FDA’s roadmap encourages leveraging organoids alongside computational models to predict drug toxicity and efficacy ⁶ . For instance, liver organoids can detect hepatotoxic effects that might be missed in animal trials, while cardiac organoids enable arrhythmia risk assessment. These systems are not only more physiologically relevant but also scalable for high-throughput screening. Wang et al. ⁷ highlighted engineered skin organoids as a robust platform for cosmetic toxicity testing, replacing traditional methods with higher sensitivity and ethical compliance. Lung organoids, particularly airway-liquid interface (ALI) models, are used to screen drugs for respiratory diseases. In addition, pluripotent stem cell (PSC)-derived lung organoids replicate primary lung structure, making them valuable for modeling diseases ⁸ .

Regenerative medicine and tissue engineering

Organoids are paving the way for breakthroughs in regenerative medicine. Research on endometrial regeneration demonstrated that multi-lineage organoids seeded on acellular amniotic membranes restored uterine function in animal models, offering hope for treating Asherman’s syndrome ⁹ . Similarly, advances in retinal organoids have accelerated therapies for inherited retinopathies, with bibliometric analyses revealing exponential growth in this field ¹⁰ . In bone tissue engineering, Qi et al. ¹¹ reviewed spatiotemporal BMP-2 delivery strategies using organoid-based scaffolds to enhance bone regeneration while minimizing side effects.

Challenges and future directions

Despite their promise, organoid systems face technical and logistical hurdles. Variability in culture conditions, limited vascularization^12,13, and high costs remain barriers to widespread adoption ¹⁴ . For example, Chang et al. ¹⁵ compared conventional and conditioned media for fallopian tube organoid cultures, finding equivalent costs but differences in proliferation and gene expression. Standardizing protocols and integrating organoid-microenvironment interactions (e.g. immune cells, vasculature) will be essential for improving clinical relevance.

Conclusion

As the scientific community embraces organoid technologies, their integration into regulatory and clinical frameworks marks a pivotal step toward human-centric drug development. This special collection highlights the diverse applications of organoids in modeling diseases, screening potential therapies, and promoting tissue regeneration, demonstrating their revolutionary potential. By bridging innovation with regulatory evolution, we stand at the threshold of a new era in biomedicine, where patient-specific models drive safer, faster, and more ethical therapeutic breakthroughs.