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Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
Current Availability of Stem Cell-Based In Vitro Methods for Developmental Neurotoxicity (DNT) Testing
Ellen Fritsche1, Marta Barenys2, Jördis Klose2
1Heinrich Heine University, 40225, Düsseldorf, Germany.
Abstract:
There is evidence that chemical exposure during development can cause irreversible impairments of the human developing nervous system. Therefore, testing compounds for their developmentally neurotoxic potential has high priority for different stakeholders: academia, industry, and regulatory bodies. Due to the resource-intensity of current developmental neurotoxicity (DNT) in vivo guidelines, alternative methods that are scientifically valid and have a high predictivity for humans are especially desired by regulators. Here, we review availability of stem-/progenitor cell-based in vitro methods for DNT evaluation that is based on the concept of neurodevelopmental process assessment. These test methods are assembled into a DNT in vitro testing battery. Gaps in this testing battery addressing research needs are also pointed out.
Insights
Chemicals can harm developing nervous systems. This review explores stem cell-based in vitro methods for developmental neurotoxicity (DNT) testing, offering alternatives to resource-intensive animal studies.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Chemical exposures during development can lead to irreversible neurodevelopmental impairments.
- Assessing developmental neurotoxicity (DNT) is crucial for public health and regulatory safety.
- Current in vivo DNT guidelines are resource-intensive, driving the need for alternative methods.
Purpose of the Study:
- To review available stem/progenitor cell-based in vitro methods for DNT evaluation.
- To assess these methods based on the concept of neurodevelopmental process assessment.
- To identify research gaps within a proposed DNT in vitro testing battery.
Main Methods:
- Literature review of stem/progenitor cell-based in vitro assays for DNT.
- Assessment of methods against neurodevelopmental processes.
- Compilation of methods into a testing battery framework.
Main Results:
- Stem/progenitor cell-based in vitro methods show promise for DNT evaluation.
- These methods can assess specific neurodevelopmental processes.
- Gaps exist in the current testing battery, highlighting areas for future research.
Conclusions:
- In vitro cell-based assays offer a viable alternative to traditional DNT testing.
- A comprehensive DNT in vitro testing battery is being developed.
- Further research is needed to fill identified gaps and validate these alternative methods.
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