Exploring Environmental Neurotoxicity Assessment Using Human Stem Cell-Derived Models
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Abstract
Neurotoxicity is increasingly recognized as a critical factor impacting long-term health, with growing evidence linking it to both neurodevelopmental and neurodegenerative diseases. Pesticides, widely used in agriculture and industry, have emerged as significant contributors to neurotoxic risk, given their capacity to disrupt key neurodevelopmental processes at low exposure levels. As conventional animal models present limitations in interspecies translation, human-derived neuron-based in vitro screening strategies are urgently needed to assess potential toxicants accurately. Human-induced pluripotent stem cells (hiPSCs) offer an innovative and scalable source for human-specific neuronal models that complement traditional animal-based approaches and support the development of predictive assays for neurotoxicity. Recent various stem cell models, including 2D cultures, 3D organoids, and microfluidic systems, are now available, advancing predictive neurotoxicology by simulating key aspects of human neural development and function. With the integration of High-Throughput (HT) and High-Content (HC) screening methodologies, these hiPSC-based systems enable efficient, large-scale evaluation of chemical effects on neural cells, enhancing our ability to detect early biomarkers of neurotoxic effects. Identifying early biomarkers of neurotoxic is essential to developing therapeutic interventions before irreversible damage occurs. This is particularly crucial in the context of developmental neurotoxicity, where early exposure to toxicants can have lifelong consequences. This review specifically presents an in-depth overview of the current progress in hiPSC-derived neural models and their applications in neurotoxicity testing, with a specific focus on their utility in assessing pesticide-induced neurotoxicity. Emphasizing future research priorities, we highlight the potential of these models to transform predictive toxicology, offering more human-relevant assessments and advancing the field toward a more precise evaluation of environmental neurotoxicants.
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