Investigating the Effects of FDA-approved Drugs in a Cortical Organoid Model of Neurodevelopment
Abstract/Contents
- Abstract
- The effects of many FDA-approved drugs on the development of the human brain are still poorly understood. Despite an extensive review process, verification of drug safety is often carried out in animal models, and later clinical trials tend to exclude pregnant women. For these reasons, new ways of evaluating the effects of drugs on early neurodevelopment in human cells are needed. Neural organoids derived from pluripotent stem cells present an excellent model system for studying brain development and dysfunction in human cells, but large-scale organoid culture has been difficult to maintain. In this study, I used a biocompatible polymer co-culture approach, which allows many organoids to be cultured simultaneously, to perform a screen investigating the effects of 298 drugs including FDA-approved compounds and teratogens on early cortical development in over 2,400 cortical organoids. Examining organoid growth over time, cytotoxicity, and distribution of a key neurodevelopmental marker allowed identification of a known teratogen affecting cortical organoid growth and development. I also found an intriguing result regarding the effect of a class of serotonin receptor agonists known as triptans on organoid growth. Taken together, the results of this study provide an evaluation of the effects of a wide variety of FDA-approved drugs on early cortical development and demonstrate the utility of cortical organoids for large-scale drug screens in the future.
Description
| Type of resource | text |
|---|---|
| Date modified | December 5, 2022 |
| Publication date | May 6, 2022; May 2022 |
Creators/Contributors
| Author | Pavlov, Sergey |
|---|---|
| Thesis advisor | Pașca, Sergiu |
| Thesis advisor | Chen, Xiaoke |
| Degree granting institution | Stanford University, Department of Biology |
Subjects
| Subject | Biology |
|---|---|
| Subject | Organoid |
| Subject | High throughput screening (Drug development) |
| Subject | Neurodevelopment |
| Subject | Serotonin > Agonists |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
Access conditions
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 4.0 International license (CC BY-NC).
Preferred citation
- Preferred citation
- Pavlov, S., Pașca, S. (2022). Investigating the Effects of FDA-approved Drugs in a Cortical Organoid Model of Neurodevelopment. Stanford Digital Repository. Available at https://purl.stanford.edu/ny822xq0203
Collection
Undergraduate Theses, Department of Biology, 2021-2022
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- Contact
- sergeyp@stanford.edu
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