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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Stem Cells for Next Level Toxicity Testing in the 21st Century
Ellen Fritsche1,2, Thomas Haarmann-Stemmann1, Julia Kapr1
1IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, 40225, Germany.
Abstract:
The call for a paradigm change in toxicology from the United States National Research Council in 2007 initiates awareness for the invention and use of human-relevant alternative methods for toxicological hazard assessment. Simple 2D in vitro systems may serve as first screening tools, however, recent developments infer the need for more complex, multicellular organotypic models, which are superior in mimicking the complexity of human organs. In this review article most critical organs for toxicity assessment, i.e., skin, brain, thyroid system, lung, heart, liver, kidney, and intestine are discussed with regards to their functions in health and disease. Embracing the manifold modes-of-action how xenobiotic compounds can interfere with physiological organ functions and cause toxicity, the need for translation of such multifaceted organ features into the dish seems obvious. Currently used in vitro methods for toxicological applications and ongoing developments not yet arrived in toxicity testing are discussed, especially highlighting the potential of models based on embryonic stem cells and induced pluripotent stem cells of human origin. Finally, the application of innovative technologies like organs-on-a-chip and genome editing point toward a toxicological paradigm change moves into action.
Insights
This review highlights the shift towards human-relevant alternative methods for toxicology testing. Advanced organotypic models and innovative technologies are crucial for accurate toxicological hazard assessment.
Area of Science:
- Toxicology and Pharmacology
- Biomedical Engineering
- Stem Cell Biology
Background:
- The 2007 US National Research Council report called for a paradigm shift in toxicology.
- Traditional 2D in vitro models are insufficient for complex human organ mimicry.
- There is a growing need for human-relevant alternative methods in toxicological hazard assessment.
Purpose of the Study:
- To review critical organs for toxicity assessment and their functions.
- To discuss current and emerging in vitro methods for toxicological applications.
- To highlight the potential of human stem cell-based models and advanced technologies.
Main Methods:
- Review of scientific literature on organ function and toxicity.
- Analysis of current in vitro toxicology methods.
- Exploration of emerging technologies like organs-on-a-chip and genome editing.
Main Results:
- Identified key organs (skin, brain, thyroid, lung, heart, liver, kidney, intestine) for toxicity assessment.
- Discussed limitations of current 2D in vitro systems.
- Highlighted the promise of organotypic models, human pluripotent stem cells, organs-on-a-chip, and genome editing.
Conclusions:
- A paradigm shift towards human-relevant, complex in vitro models is necessary for toxicology.
- Organotypic models and advanced technologies are essential for accurate toxicological hazard assessment.
- The integration of these methods will drive the future of toxicology testing.
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