Stem Cells for Next Level Toxicity Testing in the 21st Century

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.

Automated summary

The call for a paradigm change in toxicology initiated by the United States National Research Council in 2007 highlights the importance of human-relevant alternative methods for toxicological hazard assessment. This review article discusses critical organs such as skin, brain, and lungs in terms of their functions in health and disease, emphasizing the need for more complex organotypic models. Innovative technologies like organs-on-a-chip and genome editing are paving the way for a shift in toxicological paradigm towards more advanced and human-specific approaches.