Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
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
Citations
23
Frontiers in Artificial Intelligence, Journal Year: 2023, Volume and Issue: 6
Published: Feb. 28, 2023
The brain is arguably the most powerful computation system known. It extremely efficient in processing large amounts of information and can discern signals from noise, adapt, filter faulty all while running on only 20 watts power. human brain's efficiency, progressive learning, plasticity are unmatched by any computer system. Recent advances stem cell technology have elevated field culture to higher levels complexity, such as development three-dimensional (3D) organoids that recapitulate functionality better than traditional monolayer systems. Organoid Intelligence (OI) aims harness innate biological capabilities for biocomputing synthetic intelligence interfacing them with technology. With latest strides technology, bioengineering, machine we explore ability compute, store given (input), execute a task (output), study how this affects structural functional connections themselves. Furthermore, understanding learning generates changes patterns connectivity shed light early stages cognition brain. Investigating these concepts an enormous, multidisciplinary endeavor necessitates engagement both scientific community public. Thus, Feb 22–24 2022, Johns Hopkins University held first Workshop form OI Community lay out groundwork establishment new discipline. potential revolutionize computing, neurological research, drug was discussed, along vision roadmap its over coming decade.
Language: Английский
Citations
35
ALTEX, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even publication of animal-based OECD test guideline for DNT in 2007, a series non-animal technology workshops and conferences (starting 2005) shaped community that delivered comprehensive battery vitro methods (IVB). Its data interpretation is covered by very recent guidance (No. 377). Here, we aim to overview field, focusing on evolution strategies, role emerging technologies, impact guidelines testing. In particular, this an example targeted development animal-free approach one most complex hazards chemicals human health. These developments started literally from blank slate, with no proposed alternative available. Over decades, cutting-edge science enabled design spares animals enables throughput challenging hazard. While it evident field needs regulation, massive economic decreased cognitive capacity caused chemical exposure should be prioritized more highly. Beyond this, claim fame scientific brought understanding brain, its development, how can perturbed. Plain language summaryDevelopmental predicts hazard brain development. Comprehensive advanced strategies using now replace approaches assess large numbers accurately efficiently than approach. Recent formalized DNT, marking pivotal achievement field. The shift towards reflects both commitment animal welfare growing recognition public health impacts associated impaired function exposures. innovations ultimately contribute safer management better protection health, especially during vulnerable stages
Language: Английский
Citations
8
Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 962 - 973
Published: Jan. 11, 2024
Language: Английский
Citations
5
Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 674 - 674
Published: April 13, 2024
Oligodendrocytes originating in the brain and spinal cord as well ventral dorsal domains of neural tube are transcriptomically functionally distinct. These distinctions also reflected ultrastructure produced myelin, susceptibility to myelin-related disorders, which highlights significance choice patterning protocols differentiation induced pluripotent stem cells (iPSCs) into oligodendrocytes. Thus, our first goal was survey different approaches applied generation iPSC-derived oligodendrocytes 2D culture organoids, reflect on how these pertain regional spatial fate generated oligodendrocyte progenitors myelinating This knowledge is increasingly important disease modeling future therapeutic strategies. Our second recap recent advances development oligodendrocyte-enriched we explore their relevance a specification alongside duration, complexity, maturation stages myelin biology. Finally, discuss shortcomings existing potential explorations.
Language: Английский
Citations
5
Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(8), P. 101680 - 101680
Published: Aug. 1, 2024
The role of central nervous system (CNS) glia in sustaining self-autonomous inflammation and driving clinical progression multiple sclerosis (MS) is gaining scientific interest. We applied a single transcription factor (SOX10)-based protocol to accelerate oligodendrocyte differentiation from human induced pluripotent stem cell (hiPSC)-derived neural precursor cells, generating self-organizing forebrain organoids. These organoids include neurons, astrocytes, oligodendroglia, hiPSC-derived microglia achieve immunocompetence. Over 8 weeks, reproducibly generated mature CNS types, exhibiting single-cell transcriptional profiles similar the adult brain. Exposed inflamed cerebrospinal fluid (CSF) patients with MS, properly mimic macroglia-microglia neurodegenerative phenotypes intercellular communication seen chronic active MS. Oligodendrocyte vulnerability emerged by day 6 post-MS-CSF exposure, nearly 50% reduction. Temporally resolved organoid data support expand on soluble CSF mediators downstream events leading death inflammatory neurodegeneration. Such findings implementation this model for drug screening halt
Language: Английский
Citations
5
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 19, 2024
Summary Brain Microphysiological Systems including neural organoids derived from human induced pluripotent stem cells offer a unique lens to study the intricate workings of brain. This paper investigates foundational elements learning and memory in organoids, also known as Organoid Intelligence by quantifying immediate early gene expression, synaptic plasticity, neuronal network dynamics, criticality demonstrate utility these basic science research. Neural showed synapse formation, glutamatergic GABAergic receptor expression basally evoked, functional connectivity, criticality, plasticity response theta-burst stimulation. In addition, pharmacological interventions on receptors, input specific stimulation further shed light capacity mirror modulation short-term potentiation, demonstrating their potential tools for studying neurophysiological neurological processes informing therapeutic strategies diseases. Graphical Abstract Overview main components experiments conducted. Figure created using BioRender.com.
Language: Английский
Citations
4
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 21, 2025
Abstract Brain organoid technology has revolutionized our ability to model human neurodevelopment in vitro. However, current techniques remain limited by their reliance on simplified endothelial cell populations rather than a complete system. We engineered Multi-Region Organoids (MRBOs) that integrate cerebral, mid/hindbrain, and complex organoids into one structure. Different from the earlier approaches based isolated HUVECs, contain diverse vascular types, including progenitors, mature cells, pericytes, proliferating angiogenic cells stromal cells. Our strategy employs sequential modulation of key developmental pathways generate individual organoids, followed optimized fusion conditions maintain regional identities while supporting cellular integration. Single-nucleus RNA sequencing shows MRBOs develop discrete neural specific each brain region alongside specialized establish paracrine signalling networks. Integration analysis with fetal data contribute 80% clusters found tissue (Carnegie stages 12-16), whereas CellChat identifies 13 previously uncharacterized endothelial-neural interactions. Notably, we uncover endothelial-derived factors support persistence intermediate progenitor during hindbrain development, but not cerebral thereby revealing new role for patterning. This platform enables matching multiple regions, fully incorporating nature at same time providing opportunities studying neurodevelopmental disorders which neural-endothelial interactions are disrupted. MRBO system establishes foundation investigating processes, an enabling context closer physiological relevance.
Language: Английский
Citations
0
Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)
Published: April 22, 2025
Glioblastoma multiforme (GBM) is the foremost prevalent and highly aggressive intracranial malignancy, which urgently needs safer more efficacious therapeutic strategies. Our research aimed to investigate impact underlying mechanism of Taurochenodeoxycholic acid (TCDCA) on GBM. In this study, we explored suppressive effect TCDCA in vitro by qualification proliferation migration assays flow cytometry, subsequently predicted potential anti-GBM mRNA sequencing following rescue experiments. An orthotopic GBM model C57BL/6 mice further demonstrated TCDCA. experiments verified that inhibited growth cells induced cell cycle arrest at G2/M phase. Subsequent investigations showed upregulation HMGCS1 HMGCR downregulation glutathione peroxidase-4 (GPX4) was observed treatment. Notably, inhibitory effects as well induction ferroptosis were partially restored Simvastatin (SIN), a competitive inhibitor. Furthermore, an transplantation vivo. impedes progression virtue intricately orchestrated molecular cascade, through HMGCS1/HMGCR/GPX4 signaling axis, thus unveiling novel avenue warranting scrutiny treatment landscape
Language: Английский
Citations
0
Toxicologic Pathology, Journal Year: 2025, Volume and Issue: unknown
Published: May 15, 2025
The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on “New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives,” organized in Spain, addressed the growing need improved assessment neurotoxicity. Traditional neurotoxicity using vivo animal studies are impractical testing substantial number environmental chemicals that currently lack data early detection neuro-related adverse reactions drug discovery. NAMs, including human vitro assays small model organisms, have been developed faster cost-effective neurotoxic potential. While NAMs offer practicality, utility, valuable mechanistic insights, their integration into regulatory decision-making requires robust scientific validation technical characterization. Confidence application can be supported by mapping cellular outcomes to neuropathological findings mammals, humans, through Adverse Outcome Pathway (AOP) framework, Integrated Testing (IATA). Case presented demonstrated chemical safety evaluations, focusing developmental (DNT), Parkinson’s disease, drug-induced seizures. In conjunction with toxicology studies, represent a significant step toward advancing toxicity via hazard identification screening assessments.
Language: Английский
Citations
0