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Neurotoxicants are substances that can lead to adverse structural or functional effects on the nervous system. These can be chemical, biological, or physical agents that can cross the blood brain barrier to damage neurons or interferewith complex interactions between the nervous system and other organs. With concerns regarding social policy, public health, andmedicine, there is a need to ensure rigorous testing for neurotoxicity. While the most common neurotoxicity tests involve using animal models, a shift towards stem cell-based platforms can potentially provide a more biologically accurate alternative in both clinical and pharmaceutical research. With this in mind, the objective of this article is to review both current technologies and recent advancements in evaluating neurotoxicants using stem cell-based approaches, with an emphasis on developmental neurotoxicants (DNTs) as these have the most potential to lead to irreversible critical damage on brain function. In the next section, attempts to develop novel predictive model approaches for the study of both neural cell fate and developmental neurotoxicity are discussed. Finally, this article concludes with a discussion of the future use of in silico methods within developmental neurotoxicity testing, and the role of regulatory bodies in promoting advancementswithin the space. [ABSTRACT FROM AUTHOR]

Controlled delivery of proteins has immense potential for the treatment of various human diseases, but effective strategies for their delivery are required before this potential can be fully realized. Recent research has identified hydrogels as a promising option for the controlled delivery of therapeutic proteins, owing to their ability to respond to diverse chemical and biological stimuli, as well as their customizable properties that allow for desired delivery rates. This study utilized alginate and chitosan as model polymers to investigate the effects of hydrogel properties on protein release rates. The results demonstrated that polymer properties, concentration, and crosslinking density, as well as their responses to pH, can be tailored to regulate protein release rates. The study also revealed that hydrogels may be combined to create double-network hydrogels to provide an additional metric to control protein release rates. Furthermore, the hydrogel scaffolds were also found to preserve the long-term function and structure of encapsulated proteins before their release from the hydrogels. In conclusion, this research demonstrates the significance of integrating porosity and response to stimuli as orthogonal control parameters when designing hydrogel-based scaffolds for therapeutic protein release. [ABSTRACT FROM AUTHOR]

Gene delivery to, and gene targeting in, stem cells would be a highly enabling technology for basic science and biomedical application. Adeno-associated viral (AAV) vectors have demonstrated the capacity for efficient delivery to numerous cells, but their application to stem cells has been limited by low transduction efficiency. Due to their considerable advantages, however, engineering AAV delivery systems to enhance gene delivery to stem cells may have an impact in stem cell biology and therapy. Therefore, using several diverse AAV capsid libraries-including randomly mutagenized, DNA shuffled, and random peptide insertion variants-we applied directed evolution to create a 'designer' AAV vector with enhanced delivery efficiency for neural stem cells (NSCs). A novel AAV variant, carrying an insertion of a selected peptide sequence on the surface of the threefold spike within the heparin-binding site, emerged from this evolution. Importantly, this evolved AAV variant mediated efficient gene delivery to rat, mouse, and human NSCs, as well as efficient gene targeting within adult NSCs, and it is thus promising for applications ranging from basic stem cell biology to clinical translation. [ABSTRACT FROM AUTHOR]

The ability to introduce precise genomic modifications in human cells has profound implications for both basic and applied research in stem cells, ranging from identification of genes regulating stem cell self-renewal and multilineage differentiation to therapeutic gene correction and creation of in vitro models of human diseases. However, the overall efficiency of this process is challenged by several factors including inefficient gene delivery into stem cells and low rates of homology directed site-specific targeting. Recent studies report the development of novel techniques to improve gene targeting efficiencies in human stem cells; these methods include molecular engineering of viral vectors to efficiently deliver episomal genetic sequences that can participate in homology directed targeting, as well as the design of synthetic proteins that can introduce double-stranded breaks in DNA to initiate such recombination events. This review focuses on the potential of these new technologies to precisely alter the human stem cell genome and also highlights the possibilities offered by the combination of these complementary strategies.