Human Biology, Better Medicines: Advancing iPSC-Based Models for Discovery and Development
Induced pluripotent stem cell (iPSC) technology has transformed biomedicine far beyond its original promise for regenerative medicine. By preserving a patient’s genetic background while enabling the generation of disease-relevant cell types—and increasingly sophisticated tissue architectures such as organoids and other advanced in vitro systems—we can now recreate key aspects of human pathology in the laboratory. These platforms are becoming a powerful engine not only for mechanistic disease research, but also for drug discovery and development.
A persistent challenge in traditional drug development has been the high failure rate in clinical trials. The primary drivers are well known: insufficient efficacy and the limited ability of preclinical models to predict human disease biology with adequate fidelity. Patient-derived iPSC models help address this translational gap in three important ways.
First, they enable “disease in a dish” by capturing human disease phenotypes directly. When carefully designed, iPSC-based systems can retain patient-specific genomic context and, in many cases, reflect the polygenic architecture that contributes to complex disorders. Second, they provide “humanity in a dish”—the ability to model inter-individual variability and patient diversity—thereby strengthening the scientific foundations for precision medicine and more rational trial stratification. Third, iPSC-based platforms offer distinct advantages for drug discovery: scalable screening and deep molecular and cellular profiling that can reveal actionable mechanisms, response biomarkers, and potential safety signals early in the pipeline.
Recognizing the rapid momentum and the need for shared standards, ISSCR recently launched the Consortium on Advanced Stem Cell-Based Models in Drug Discovery and Development, co-chaired by Shuibing Chen (Weill Cornell Medicine, USA) and Daniela Cornacchia (AstraZeneca, Sweden). The consortium provides a structured forum to accelerate responsible adoption, benchmarking, and cross-sector learning—bringing together academia, industry, and other stakeholders to define what “fit-for-purpose” should mean for advanced stem cell-based models in real-world decision-making.
In parallel, regulators are signaling an important shift toward integrating New Approach Methodologies (NAMs). In April 2025, the U.S. FDA stated that animal testing requirements will be “reduced, refined, or potentially replaced” using a range of approaches, including AI-based computational models and cell line/organoid-based testing. This is a significant development: it reflects growing confidence that human-relevant methods can strengthen preclinical evidence packages, while also encouraging innovation in how we evaluate efficacy and safety.
At the same time, we should be clear-eyed about current limitations. iPSC- and organoid-based systems—even as they continue to mature—may not fully capture multi-organ physiology, systemic immune–metabolic interactions, or whole-organism pharmacokinetics and toxicity. For many questions, in vitro human models and in vivo animal studies should be viewed as complementary rather than competing. The most reliable path toward successful clinical translation will often come from integrating the strengths of both: mechanistic precision and human genetic relevance on the one hand, and system-level physiology on the other. Our collective task is not to champion a single platform, but to build evidence frameworks that are rigorous, transparent, and predictive—so that promising therapies reach patients faster, and late-stage failures become less frequent.
This global momentum is also evident in Japan. The Japan Disease Stem Cell Society (JDSCS) was established in 2025 to advance disease stem cell research and support its societal implementation, and its first annual meeting was held on 17 February 2026 in Tokyo. These developments underscore the field’s expanding reach and the shared sense—across countries and sectors—that advanced human model systems are becoming central to the next generation of biomedical discovery.
As we move forward, the ISSCR will continue to support excellence in stem cell science and its translation to human health—by fostering collaboration, promoting standards and best practices, and engaging constructively with regulators and the public. The promise is clear: when we pair human-relevant models with rigorous validation and thoughtful integration across experimental systems, we improve not only our science, but also our chances of delivering meaningful therapies to patients worldwide.
Hideyuki Okano