Sponsored content brought to you by

Human induced pluripotent stem cells (hiPSCs) have revolutionized biomedical research by offering a versatile, human-relevant platform for modeling biology and advancing therapeutic development. Their ability to be generated from any somatic tissue, along with the potential for genome editing and differentiation into nearly any human cell type, makes them a powerful tool across multiple stages of the drug development process.

As the field evolves, the focus is shifting from initial adoption to the strategic integration of hiPSC-based models within existing drug development workflows­—aiming to enhance decision-making throughout the pipeline.

Disease modeling & target identification

hiPSC disease models can be generated from individuals carrying disease-associated mutations or by introducing specific genetic variants into healthy reference lines. Importantly, these mutations can be corrected back to wild-type to create isogenic pairs, enabling precise and controlled comparisons. This genetic matching allows researchers to isolate and investigate the functional impact of genetic changes in a human cellular context, uncover dysregulated pathways, and identify molecular targets for therapeutic intervention.

Target validation

Once potential therapeutic targets are identified, hiPSC-derived models provide a robust in vitro platform for early-stage target validation. By manipulating gene expression or applying candidate compounds in disease-relevant, hiPSC-differentiated cell types, researchers can assess whether modulating a target produces meaningful changes in cellular phenotype or disease-associated markers. This step is essential for determining which targets are associated with disease and also actionable, enabling identification of priority targets for further preclinical drug development.

Lead discovery

Once a target is identified, hiPSC-derived models can be used for compound screening and early-stage drug validation, offering a human-relevant platform for evaluating therapeutic candidates.

Leveraging genetically stable isogenic hiPSC panels—cells engineered to carry distinct mutations while sharing the same genetic background—enables direct comparison of drug effects across variants. This approach supports consistent application of growth and differentiation protocols, facilitates scalability, reduces variability, and enhances reproducibility, while allowing for precise interpretation of variant-

specific responses.

Incorporating revertant controls, where engineered mutations are corrected back to wild-type, further strengthens target specificity by confirming that observed effects are mutation-driven and not due to off-target effects. Together, these strategies minimize confounding variables and support robust lead identification and prioritization.

Preclinical testing

In preclinical studies, hiPSCs complement traditional animal models by offering insights into human-specific biology. They are particularly valuable for modeling diseases that lack robust animal models, such as certain rare genetic disorders.

Using hiPSC lines to develop complex models—such as organ-on-chip systems—helps bridge the gap between simple in vitro assays and in vivo studies. These platforms provide more human-relevant assessments of drug efficacy, toxicity, and pharmacodynamics, ultimately reducing late-stage failures and increasing confidence in candidate selection.

Clinical translation

hiPSC models play a critical role in informing drug development by helping to identify predictive biomarkers, stratify patient populations, and anticipate variability in drug response. Lines derived from diverse genetic backgrounds can reveal population-specific effects that may not be captured otherwise, supporting the development of more inclusive and personalized therapies.

Looking ahead

As hiPSC technologies advance, their impact on drug development continues to grow. Innovations in differentiation, high-content phenotyping, and complex models are improving our ability to model patient-specific biology with greater precision and relevance—driving progress in discovery, validation, and translational research.

However, successful implementation hinges on the availability of high-quality hiPSC lines and standardized protocols to ensure data reliability and reproducibility. Resources like The Jackson Laboratory hiPSC catalog support this progress by offering well-characterized isogenic lines and validated protocols, helping researchers streamline workflows, improve reproducibility, and accelerate the integration of hiPSC-based systems into diverse therapeutic pipelines.

Learn more www.jax.org/ipsc.