<p>Animal models have long been central to biomedical research, yet their limited translatability and ethical constraints underscore the need for human relevant systems in pharmacology and drug development. Organoids three dimensional, self-organizing structures derived from pluripotent, adult, or patient stem cells have emerged as transformative platforms that recapitulate the cellular diversity, architecture, and functional properties of human tissues. Advances in culture technologies, including submerged systems, air liquid interface methods, and microfluidic organ-on-chip models, have enhanced their physiological relevance and predictive drug response. Organoids are now applied across diverse domains, including genetic, neurological, metabolic, infectious, and oncological diseases, offering mechanistic insights into human pathophysiology and pharmacodynamics. Patient derived organoids, in particular, are advancing precision medicine through individualized drug response profiling, toxicity prediction, and high throughput pharmacological screening. Integration with tools such as CRISPR based genome editing, artificial intelligence, and bioengineering further expands their role in functional genomics, disease modeling, and drug mechanism studies.Despite these advances, challenges persist, including lack of vascularization and immune components, variability across batches, and incomplete tissue maturation, which currently limit broader translational adoption. Emerging strategies such as vascularized and immune competent systems, multi organoid co cultures, and AI driven optimization hold promise in overcoming these barriers. Overall, organoids represent a paradigm shift away from animal models toward ethically sound, physiologically relevant, and predictive human systems with the potential to transform drug discovery, pharmacological research, and personalized therapeutics.</p> Graphical Abstract <p></p>

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Translating Pharmacology from Animal Models to Organoids: Advancing Predictive Human Biology in Drug Discovery

  • Geeta Patel,
  • Heli Amin

摘要

Animal models have long been central to biomedical research, yet their limited translatability and ethical constraints underscore the need for human relevant systems in pharmacology and drug development. Organoids three dimensional, self-organizing structures derived from pluripotent, adult, or patient stem cells have emerged as transformative platforms that recapitulate the cellular diversity, architecture, and functional properties of human tissues. Advances in culture technologies, including submerged systems, air liquid interface methods, and microfluidic organ-on-chip models, have enhanced their physiological relevance and predictive drug response. Organoids are now applied across diverse domains, including genetic, neurological, metabolic, infectious, and oncological diseases, offering mechanistic insights into human pathophysiology and pharmacodynamics. Patient derived organoids, in particular, are advancing precision medicine through individualized drug response profiling, toxicity prediction, and high throughput pharmacological screening. Integration with tools such as CRISPR based genome editing, artificial intelligence, and bioengineering further expands their role in functional genomics, disease modeling, and drug mechanism studies.Despite these advances, challenges persist, including lack of vascularization and immune components, variability across batches, and incomplete tissue maturation, which currently limit broader translational adoption. Emerging strategies such as vascularized and immune competent systems, multi organoid co cultures, and AI driven optimization hold promise in overcoming these barriers. Overall, organoids represent a paradigm shift away from animal models toward ethically sound, physiologically relevant, and predictive human systems with the potential to transform drug discovery, pharmacological research, and personalized therapeutics.

Graphical Abstract