Impact of environmental neurotoxic: current methods and usefulness of human stem cells

Abstract

The development of central nervous system is a highly coordinated and complex process. Any alteration of this process can lead to disturbances in the structure and function of the brain, which can cause deficits in neurological development, resulting in neurodevelopmental disorders, including, for example, autism or attention-deficit hyperactivity disorder. Exposure to certain chemicals during the fetal period and childhood is known to cause developmental neurotoxicity and has serious consequences that persist into adult life. For regulatory purposes, determination of the potential for developmental neurotoxicity is performed according the OECD Guideline 426, in which the test substance is administered to animals during gestation and lactation. However, these animal models are expensive, long-time consuming and may not reflect the physiology in humans; that makes it an unsustainable model to test the large amount of existing chemical products, hence alternative models to the use of animals are needed. One of the most promising methods is based on the use of stem cell technology. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into more specialized cell types. Because of these properties, these cells have gained increased attention as possible therapeutic agents or as disease models. Here, we provide an overview of the current models both animal and cellular, available to study developmental neurotoxicity and review in more detail the usefulness of human stem cells, their properties and how they are becoming an alternative to evaluate and study the mechanisms of action of different environmental toxicants.

Advances in Alzheimer’s Disease Research: Human Cerebral Organoids

“…By definition, stem cells are those cells that remain in an undifferentiated state, have the ability of self-renewing and they can proliferate and differentiate to give rise to different cell lines according to their potency. The most used nowadays are pluripotent stem cells (PSCs) and multipotent stem cells (MSCs) [28].…”

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

“…In Group C however, there is a suggestion that the animal initially respond differently to the novel environment and that exploratory activity may be delayed and within the time frame acclimation was not evident but suggested. been reviewed in recent articles (Rosca et al, 2020; as have limitations (US EPA, 1994a). Given the focus of the current special issue it is anticipated that many of these model systems proposed for neurotoxicity assessment will be discussed in methodological detail in other articles.…”

“…While these systems offer an important approach to address issues of neurotoxicity, they are not devoid of limitations that require attention if these systems are to be put forth as a stand-alone approach to evaluate potential for human neurotoxicity. The applicability of these systems to address questions related to neurotoxicity and developmental neurotoxicity screening has been reviewed in recent articles ( Rosca et al, 2020 ; Sachana et al, 2021 ) as have limitations ( US EPA, 1994a ). Given the focus of the current special issue it is anticipated that many of these model systems proposed for neurotoxicity assessment will be discussed in methodological detail in other articles.…”

Human Embryos, Induced Pluripotent Stem Cells, and Organoids: Models to Assess the Effects of Environmental Plastic Pollution

“…Also, 3D organoids go through multi-lineage differentiation, creating heterogeneous groups of cells that self-assemble into complex tissue-like structures mimicking physiologically more pertinent microenvironment (Cugola et al, 2016). Many studies show that hESCs and hiPSCs are used for generating 2D and 3D organoids allowing the study of differentiation mechanisms (Pamies et al, 2017;Rosca et al, 2020), the processes involved in embryonic development (Lancaster and Knoblich, 2014;Pamies et al, 2017;Rosca et al, 2020), and the mechanisms involved in various diseases (Lancaster and Knoblich, 2014;Pamies et al, 2017;Rosca et al, 2020;Stojkovic et al, 2021a), drug testing (Lancaster and Knoblich, 2014), and toxicity connected with environmental pollutants (Truskey, 2018;Rosca et al, 2020;Stojkovic et al, 2021b). However, it is well known that organoids have tremendous potential in drug screening and personalized medicine (Kondo and Inoue, 2019;.…”