Curated Papers > In recent years, high-impact research on "organoids" (Impact Factor ≥ 30, last 5 years)

Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.

Literature Information

DOI	10.1038/s41573-025-01317-y
PMID	41225057
Journal	Nature reviews. Drug discovery
Impact Factor	101.8
JCR Quartile	Q1
Publication Year	2025
Times Cited	0
Keywords	Organoids, Drug Discovery, 3D Culture, Disease Modeling, Drug Screening
Literature Type	Journal Article, Review
ISSN	1474-1776
Authors	Daisong Wang, Remi Villenave, Nadine Stokar-Regenscheit, Hans Clevers

TL;DR

This review highlights the potential of organoids, three-dimensional structures derived from stem cells, as advanced models for drug discovery due to their ability to mimic human tissue complexity and heterogeneity. It discusses methodologies for organoid generation, their applications in disease modeling and drug testing, and the regulatory challenges that need to be addressed for broader implementation in pharmaceutical research.

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Organoids · Drug Discovery · 3D Culture · Disease Modeling · Drug Screening

Abstract

Organoids are 3D structures derived from stem cells that recapitulate key architectural and functional aspects of the corresponding tissue. Compared with conventional 2D cell lines, human organoids provide experimental models that more closely reflect human physiology. Their ability to capture the complexity and heterogeneity of human tissues enables the study of disease mechanisms, drug efficacy and toxicity. When generated from patient material, organoids also allow the assessment of individual drug responses. In this Review, we explore the utility of organoids in drug discovery. We outline current methodologies for generating and maintaining organoids, examine their applications in disease modelling, drug screening and safety evaluation, and consider regulatory aspects and the challenges for their broader adoption in drug discovery.

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Primary Questions Addressed

1. What specific diseases have shown the most promise in being modeled using human organoids for drug discovery?
2. How do the methodologies for generating organoids vary across different types of tissues or diseases?
3. In what ways do organoids improve the predictability of drug responses compared to traditional 2D cell lines?
4. What are the main regulatory hurdles that need to be addressed for the widespread adoption of organoids in clinical drug testing?
5. How can patient-derived organoids contribute to personalized medicine in the context of drug discovery and treatment?

Key Findings

Research Background and Objectives

Organoids are three-dimensional (3D) structures derived from stem cells that mimic the architecture and function of corresponding human tissues. Unlike traditional two-dimensional (2D) cell lines, human organoids offer experimental models that more accurately reflect human physiology. This review aims to explore the potential of organoids in drug discovery, highlighting their utility in disease modeling, drug screening, and safety evaluation.

Main Methods/Materials/Experimental Design

The review discusses various methodologies for generating and maintaining organoids, emphasizing their importance in research. The following flowchart summarizes the technical route for organoid development and application:

1. Stem Cell Isolation: The process begins with the isolation of stem cells from various sources, including patient tissues.
2. Organoid Culture: Isolated stem cells are cultured in specific conditions that promote 3D organoid formation.
3. Characterization of Organoids: Organoids are characterized to ensure they accurately reflect the original tissue in terms of architecture and function.
4. Applications:
   • Disease Modeling: Organoids are used to study disease mechanisms.
   • Drug Screening: They serve as platforms for testing drug efficacy.
   • Safety Evaluation: Organoids are employed to assess drug toxicity.

Key Results and Findings

The review highlights several key findings regarding the use of organoids in drug discovery:

• Enhanced Physiological Relevance: Organoids maintain the complexity and heterogeneity of human tissues, leading to more relevant experimental outcomes compared to 2D models.
• Personalized Medicine: Organoids derived from patient material enable the assessment of individual drug responses, paving the way for personalized therapeutic approaches.
• Regulatory Considerations: The review addresses the regulatory challenges associated with the adoption of organoids in drug discovery, emphasizing the need for standardized protocols.

Main Conclusions/Significance/Innovation

The use of organoids represents a significant advancement in biomedical research and drug discovery. Their ability to closely mimic human physiology allows for a better understanding of disease mechanisms and the development of more effective and safer drugs. The innovation lies in their potential to transform personalized medicine by providing tailored drug response assessments based on individual patient organoids.

Research Limitations and Future Directions

While organoids offer numerous advantages, several limitations and challenges remain:

• Technical Limitations: The complexity of organoid culture and maintenance can hinder widespread adoption.
• Variability: Differences in organoid formation and behavior can arise from variations in stem cell sources and culture conditions.
• Regulatory Hurdles: The integration of organoids into the drug discovery pipeline faces regulatory challenges that need to be addressed.

Future Directions:

• Standardization of organoid protocols to enhance reproducibility and reliability.
• Development of high-throughput screening methods using organoids for drug discovery.
• Exploration of organoid applications in other areas of research, such as regenerative medicine and cancer therapy.

In conclusion, organoids hold great promise in advancing drug discovery and personalized medicine, though further research and standardization are required to overcome existing challenges.

References

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