Advancing Organoid Technologies for Drug Development

automated mass characterization

The continued need for drug discovery requires extensive R&D to bring these products to market. Many drugs that make it through drug development ultimately do not pass clinical trials. The expense of screening and developing drug candidates necessitates cost-effective technologies for drug candidate screening that are more accurate to human physiology.

Currently, screening potential candidates is primarily accomplished through 2D culture bioassays and animal models, which provide information on drug safety, toxicity, efficacy and pharmacokinetic action. However, the failure rate of drugs in clinical trials remains high:

Human organoids are 3D cell cultures that develop into structures, modeling the complex structure and function of tissues and organs. They are derived from stem cells, iPSCs or cancerous tumor tissues¹'². Following cell isolation and culture under 2D conditions, the cells are embedded in an extracellular matrix, such as Matrigel, which provides an environment for them to grow and organize into 3D structures.

Combined with maintenance and monitoring, these processes can take multiple weeks, making organoid cultures more time-consuming compared to 2D studies. Nevertheless, organoids offer several key advantages:

The biopharmaceutical industry is eagerly adopting organoid systems, using cerebral and lung organoids to mimic characteristics of diseases such as Alzheimer's or cystic fibrosis, respectively. These 3D systems are also implemented in cancer research, where the biopsies collected from patients can be cultivated into ‘tumoroids’. These can be used to develop personalized oncology treatments.

While the markets for drugs such as small molecules are mature, using organoids for screening is still in development and currently faces several limitations, including reproducibility, standardization and scalability³:

These challenges must be addressed for organoids to become a reliable and scalable solution in drug screening workflows.

The Life Sciences companies of Danaher offer solutions for automating 3D cell culture, real-time data analysis and tracking organoid cultures, speeding up decision-making and enhancing the accuracy of preclinical small molecule drug screening. To learn more about improving your workflows by bringing organoid models and 3D cell culture processes into your lab, visit our Human Relevant Model and Spatial Profiling solutions or contact an expert from the Life Sciences companies of Danaher.

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References

  1. 1. Vandana JJ, Manrique C, Lacko LA, et al. Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation. Cell Stem Cell 2023; 30(5):571–91.
  2. Miranda CC, Cabral JMS. Organoids for cell therapy and drug discovery. In: Precision Medicine for Investigators, Practitioners and Providers [Internet]. Elsevier; 2020. p. 461–71.
  3. Matsui T, Shinozawa T. Human Organoids for Predictive Toxicology Research and Drug Development. Front Genet 2021; 12:1–14.
  4. Co JY, Klein JA, Kang S, Homan KA. Toward Inclusivity in Preclinical Drug Development: A Proposition to Start with Intestinal Organoids. Adv Biol 2023; 18 2200333:2200333.