Brain organoids and organoid intelligence from ethical, legal, and social points of view

Frontiers in Artificial Intelligence, Journal Year: 2024, Volume and Issue: 6

Published: Jan. 5, 2024

Human brain organoids, aka cerebral organoids or earlier "mini-brains", are 3D cellular models that recapitulate aspects of the developing human brain. They show tremendous promise for advancing our understanding neurodevelopment and neurological disorders. However, unprecedented ability to model development function

Language: Английский

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The Promise and Potential of Brain Organoids

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: Jan. 22, 2024

Brain organoids are 3D in vitro culture systems derived from human pluripotent stem cells that self-organize to model features of the (developing) brain. This review examines techniques behind organoid generation, their current and potential applications, future directions for field. possess complex architecture containing various neural cell types, synapses, myelination. They have been utilized toxicology testing, disease modeling, infection studies, personalized medicine, gene-environment interaction studies. An emerging concept termed Organoid Intelligence (OI) combines with artificial intelligence generate learning memory, goals modeling cognition enabling biological computing applications. allow neuroscience studies not previously achievable traditional techniques, transform drug development, understanding brain development disorders. The aspirational vision OI parallels origins intelligence, efforts underway map a roadmap toward its realization. In summary, constitute disruptive technology is rapidly advancing gaining traction across multiple disciplines.

Language: Английский

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Modelling metabolic diseases and drug response using stem cells and organoids

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(12), P. 744 - 759

Published: Sept. 7, 2022

Language: Английский

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Brain organoids are new tool for drug screening of neurological diseases

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 0(0), P. 0 - 0

Published: Jan. 1, 2023

At the level of in vitro drug screening, development a phenotypic analysis system with high-content screening at core provides strong platform to support high-throughput screening. There are few systematic reports on brain organoids, as new three-dimensional model, terms model stability, key fingerprint, and schemes, particularly regarding strategies for massive numbers traditional Chinese medicine monomers. This paper reviews organoids advantages over induced neurons or cells simulated diseases. The also highlights prospects from induction criteria schemes based characteristics application system.

Language: Английский

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Experimental Models of In Vitro Blood–Brain Barrier for CNS Drug Delivery: An Evolutionary Perspective

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2710 - 2710

Published: Jan. 31, 2023

Central nervous system (CNS) disorders represent one of the leading causes global health burden. Nonetheless, new therapies approved against these are among lowest compared to their counterparts. The absence reliable and efficient in vitro blood–brain barrier (BBB) models resembling vivo properties stands out as a significant roadblock developing successful therapy for CNS disorders. Therefore, advancement creation robust sensitive BBB drug screening might allow us expedite neurological development. This review discusses major developed now exploring cerebral vasculature. Our main focus is describing existing models, including 2D transwell covering both single-layer co-culture 3D organoid microfluidic with construction, permeability measurement, applications, limitations. Although better at recapitulating than other gaps still exist use predicting performance neurotherapeutics. However, this comprehensive account can be useful researchers create improved future.

Language: Английский

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Global Literature Analysis of Organoid and Organ‐on‐Chip Research

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(21)

Published: July 22, 2023

Organoids and cells in organ-on-chip platforms replicate higher-level anatomical, physiological, or pathological states of tissues organs. These technologies are widely regarded by academia, the pharmacological industry regulators as key biomedical developments. To map advances this emerging field, a literature analysis 16,000 article metadata based on quality-controlled text-mining algorithm is performed. The covers titles, keywords, abstracts categorized academic publications preprint databases published after 2010. identifies tracks 149 107 organs organ substructures modeled organoids organ-on-chip, respectively, stem cell sources, well 130 diseases, 16 groups organisms other than human mouse which organoid/organ-on-chip technology applied. illustrates changing diversity focus research captures its geographical distribution. downloadable dataset provided robust framework for researchers to interrogate with their own questions.

Language: Английский

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Advancing preclinical models of psychiatric disorders with human brain organoid cultures

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 83 - 95

Published: Aug. 10, 2022

Psychiatric disorders are often distinguished from neurological in that the former do not have characteristic lesions or findings cerebrospinal fluid, electroencephalograms (EEGs), brain imaging, and furthermore commonly recognized convergent mechanisms. involve clinical diagnosis of phenotypic behavioral disturbances mood psychosis, with a poorly understood contribution environmental factors. As such, psychiatric disease has been challenging to model preclinically for mechanistic understanding pharmaceutical development. This review compares used animal paradigms preclinical testing evolving techniques induced pluripotent cell culture focus on emerging three-dimensional models. Advances complexity 3D cultures, recapitulating electrical activity utero, modeling mood, environmentally reviewed. Insights these rapidly expanding technologies discussed as they pertain utility human organoid other models finding novel research directions, validating action, disease.

Language: Английский

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Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7435 - 7435

Published: April 18, 2023

The extracellular matrix (ECM) of the brain is a dynamic structure made up vast network bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these due to genetic variation or environmental stressors are thought affect functions may result disease. However, most mechanistic studies date usually focus on aspects diseases pay less attention relevance processes governing nature disease pathogenesis. Thus, ECM's diversified biological roles, increasing interest its involvement disease, lack sufficient compiled evidence regarding relationship with Parkinson's (PD) pathology, we aimed compile existing boost current knowledge area provide refined guidance for future research. Here, this review, gathered postmortem tissue induced pluripotent stem cell (iPSC)-related from PubMed Google Scholar identify, summarize describe common macromolecular alterations expression ECM components (PD). A literature search was conducted until 10 February 2023. overall hits database manual proteomic transcriptome were 1243 1041 articles, respectively. Following full-text articles 24 transcriptomic found be eligible inclusion. According studies, proteins such as collagens, fibronectin, annexins, tenascins recognized differentially expressed Transcriptomic displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, adhesion molecules limited number relevant accessed our search, indicating much work remains carried out better understand roles neurodegeneration believe review will elicit focused primary thus support ongoing efforts discovery development diagnostic biomarkers well therapeutic agents

Language: Английский

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Development of brain organoid technology derived from iPSC for the neurodegenerative disease modelling: a glance through

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Aug. 3, 2023

Neurodegenerative diseases are adult-onset neurological conditions that notoriously difficult to model for drug discovery and development because most models unable accurately recapitulate pathology in disease-relevant cells, making it extremely explore the potential mechanisms underlying neurodegenerative diseases. Therefore, alternative of human or animal cells have been developed bridge gap allow impact new therapeutic strategies be anticipated more by trying mimic neuronal glial cell interactions many mechanisms. In tandem with emergence human-induced pluripotent stem which were first generated 2007, accessibility (hiPSC) derived from patients can differentiated into neurons, providing an unrivaled platform

Language: Английский

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CUL4B mutations impair human cortical neurogenesis through PP2A-dependent inhibition of AKT and ERK

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 8, 2024

Mutation in CUL4B gene is one of the most common causes for X-linked intellectual disability (XLID). scaffold protein CUL4B-RING ubiquitin ligase (CRL4B) complex. While roles cancer progression and some developmental processes like adipogenesis, osteogenesis, spermatogenesis have been studied, mechanisms underlying neurological disorders patients with mutations are poorly understood. Here, using 2D neuronal culture cerebral organoids generated from patient-derived induced pluripotent stem cells their isogenic controls, we demonstrate that required to prevent premature cell cycle exit precocious differentiation neural progenitor cells. Moreover, loss-of-function lead increased synapse formation enhanced excitability. Mechanistically, CRL4B complex represses transcription PPP2R2B PPP2R2C genes, which encode two isoforms regulatory subunit phosphatase 2 A (PP2A) complex, through catalyzing monoubiquitination H2AK119 promoter regions. result upregulated PP2A activity, inhibition AKT ERK, leading exit. Activation ERK or activity mutant rescues neurogenesis defect. Our work unveils an essential role human cortical development.

Language: Английский

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