Tools for studying human microglia: In vitro and in vivo strategies

Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 107, P. 369 - 382

Published: Nov. 3, 2022

Microglia may only represent 10% of central nervous system (CNS) cells but they perform critical roles in development, homeostasis and neurological disease. are also environmentally regulated, quickly losing their transcriptomic epigenetic signature after leaving the CNS. This facet microglia biology is both fascinating technically challenging influencing study genetics function human a manner that recapitulates CNS environment. In this review we provide comprehensive overview existing vitro vivo methodology to microglia, such as immortalized lines, stem cell-derived cerebral organoids xenotransplantation. Since there currently no single method completely all hallmarks ex adult homeostatic discuss advantages limitations each model practical guide for researchers.

Language: Английский

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Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3113 - 3113

Published: Feb. 4, 2023

Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways treat disease. Organoids the liver, kidney, intestine, lung, brain been developed recent years. used for pathogenesis investigating therapeutic options neurodevelopmental, neuropsychiatric, neurodegenerative, neurological disorders. Theoretically, several disorders can be modeled with aid human organoids, hence potential exists migraine its treatment organoids. Migraine is considered a disorder non-neurological abnormalities symptoms. Both genetic environmental factors play essential roles clinical manifestations. Several types migraines classified, example, without aura, from patients these study (e.g., channelopathy calcium channels) stressors chemical mechanical). In models, drug candidates purposes also tested. Here, limitations studying communicated generate motivation stimulate curiosity further research. This must, however, alongside complexity concept neuroethical aspects topic. Interested researchers invited join network protocol development hypothesis presented here.

Language: Английский

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Direct Cell Reprogramming and Phenotypic Conversion: An Analysis of Experimental Attempts to Transform Astrocytes into Neurons in Adult Animals

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 618 - 618

Published: Feb. 14, 2023

Central nervous system (CNS) repair after injury or disease remains an unresolved problem in neurobiology research and unmet medical need. Directly reprogramming converting astrocytes to neurons (AtN) adult animals has been investigated as a potential strategy facilitate brain spinal cord recovery advance fundamental biology. Conceptually, AtN strategies rely on forced expression repression of lineage-specific transcription factors make endogenous become “induced neurons” (iNs), presumably without re-entering any pluripotent multipotent states. The AtN-derived cells have reported manifest certain neuronal functions vivo. However, this approach raised many new questions alternative explanations regarding the biological features end products (e.g., iNs versus neuron-like cells, neural functional changes, etc.), developmental biology underpinnings, neurobiological essentials. For paper per se, we proposed draw unconventional distinction between direct cell conversion reprogramming, relative somatic nuclear transfer, based experimental methods utilized initiate transformation process, aiming promote more in-depth mechanistic exploration. Moreover, summarized current tactics employed for induction, comparisons bench endeavors concerning outcome tangibility, discussion issues published protocols. Lastly, urgency clearly define/devise theoretical frameworks, bases, specifics experimentally validate primary data studies was highlighted.

Language: Английский

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iPSCs as a groundbreaking tool for the study of adverse drug reactions: A new avenue for personalized therapy

WIREs Mechanisms of Disease, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 28, 2023

Abstract Induced pluripotent stem cells (iPSCs), obtained by reprogramming different somatic cell types, represent a promising tool for the study of drug toxicities, especially in context personalized medicine. Indeed, these retain same genetic heritage donor, allowing development models. In addition, they useful adverse reactions (ADRs) special populations, such as pediatric patients, which are often poorly represented clinical trials due to ethical issues. Particularly, iPSCs can be differentiated into any tissue human body, following several protocols use stimuli induce specific differentiation processes. Differentiated also maintain and therefore suitable pharmacological studies; moreover, iPSC‐derived valuable investigation mechanisms underlying physiological iPSCs‐derived organoids another important ADRs. Precisely, vitro 3D models better native organ, both from structural functional point view. Moreover, way 2D models, appropriate since donor. comparison other present advantages terms versatility, patient‐specificity, This review aims provide an updated report employment iPSCs, derived these, article is categorized under: Cancer > Stem Cells Development

Language: Английский

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

Frontiers in Toxicology, Journal Year: 2022, Volume and Issue: 4

Published: Feb. 25, 2022

With the appreciation that behavior represents integration and complexity of nervous system, neurobehavioral phenotyping assessment has seen a renaissance over last couple decades, resulting in robust database on rodent performance within various testing paradigms, possible associations with human disorders, therapeutic interventions. The interchange data across other test modalities multiple model systems advanced our understanding fundamental biology mechanisms associated normal functions alterations system. While there is demonstrated value power assessments for examining due to genetic manipulations, maternal factors, early development environment, applied use assess environmental neurotoxicity continues come under question as whether sensitive endpoint assessment. Why tool neuroscientist yet, not when used pre-clinical or chemical studies? Applying new paradigms evidence biological basis requires expertise refinement how such experiments are conducted minimize variability maximize information. This review presents relevant issues methods conduct test, sources variability, experimental design, analysis, interpretation, reporting. It beneficial critical limitations they translate vivo environment considers need integrate disciplines best value. proposes behavioral subtle pronounced differences will facilitate obtained approaches address translation.

Language: Английский

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