Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10762 - 10762

Published: June 28, 2023

Understanding the complexities of human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations replicating intricacies, necessitating development vitro models that can simulate structure function. Three-dimensional models, including organoids, cerebral bioprinted functionalized offer promising platforms for studying development, physiology, disease. These accurately replicate key aspects anatomy, gene expression, cellular behavior, enabling drug discovery toxicology studies while providing insights into human-specific phenomena not easily studied animal models. The use human-induced pluripotent stem cells has revolutionized generation 3D structures, with various techniques developed to generate specific regions. advancements facilitate study function, overcoming previous due scarcity samples. This technical review provides an overview current cortex, their characterization, limitations, explores state art future directions field, focus on applications neurodevelopmental neurodegenerative disorders.

Language: Английский

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The Impact of the Cellular Environment and Aging on Modeling Alzheimer's Disease in 3D Cell Culture Models

Advanced Science, Journal Year: 2023, Volume and Issue: 10(8)

Published: Jan. 15, 2023

Creating a cellular model of Alzheimer's disease (AD) that accurately recapitulates pathology has been longstanding challenge. Recent studies showed human AD neural cells, integrated into three-dimensional (3D) hydrogel matrix, display key features neuropathology. Like in the brain, extracellular matrix (ECM) plays critical role determining rate neuropathogenesis hydrogel-based 3D models. Aging, greatest risk factor for AD, significantly alters brain ECM properties. Therefore, it is important to understand how age-associated changes affect accumulation pathogenic molecules, neuroinflammation, and neurodegeneration patients vitro In this review, mechanistic hypotheses presented address impact properties their with aging on AD-related dementias. Altered characteristics aged brains, including stiffness, pore size, composition, will contribute pathogenesis by modulating accumulation, propagation, spreading molecules AD. Emerging models differing provide an exciting opportunity study pathogenesis, providing novel insights. Understanding should also improve modeling systems.

Language: Английский

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Engineering brain-on-a-chip platforms

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(8), P. 691 - 709

Published: June 5, 2024

Language: Английский

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SIMS: A deep-learning label transfer tool for single-cell RNA sequencing analysis

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(6), P. 100581 - 100581

Published: May 31, 2024

Cell atlases serve as vital references for automating cell labeling in new samples, yet existing classification algorithms struggle with accuracy. Here we introduce SIMS (scalable, interpretable machine learning single cell), a low-code data-efficient pipeline single-cell RNA classification. We benchmark against datasets from different tissues and species. demonstrate SIMS's efficacy classifying cells the brain, achieving high accuracy even small training sets (<3,500 cells) across samples. accurately predicts neuronal subtypes developing shedding light on genetic changes during differentiation postmitotic fate refinement. Finally, apply to of cortical organoids predict identities uncover variations between lines. identifies cell-line differences misannotated lineages human derived pluripotent stem Altogether, show that is versatile robust tool cell-type datasets.

Language: Английский

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Brain organoid: a 3D technology for investigating cellular composition and interactions in human neurological development and disease models in vitro

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 31, 2021

Abstract The study of human brain physiology, including cellular interactions in normal and disease conditions, has been a challenge due to its complexity unavailability. Induced pluripotent stem cell (iPSC) is indispensable the pathophysiology neurological disorders. Nevertheless, monolayer systems lack cytoarchitecture necessary for modeling. Brain organoids generated from cells supply an ideal environment model both brain. This review article discusses composition among neural lineage non-central nervous system types organoids, current studies, future perspectives organoid research. Ultimately, promise unveil previously inaccessible features neurobiology that emerge complex improve our mechanistic understanding development diseases. Graphical abstract

Language: Английский

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A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies

Theranostics, Journal Year: 2022, Volume and Issue: 12(16), P. 6826 - 6847

Published: Jan. 1, 2022

Rationale:The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD).Focused ultrasound applied together with microbubbles (FUS +MB ) novel technique transiently open BBB and increase delivery.Evidence suggests that FUS safe, however, effects on human cells, especially in context AD, remain sparsely investigated.In addition, there currently are no cell platforms test -mediated delivery.Methods: Here we generated cells (induced brain endothelial-like (iBECs) astrocytes (iAstrocytes)) from apolipoprotein E gene allele E4 (APOE4, high sporadic AD risk) E3 (APOE3, lower carrying patient-derived induced pluripotent stem (iPSCs).We established mono-and co-culture models control investigate phenotype screen two potentially antibodies, an Aducanumab-analogue (Aduhelm TM ; anti-amyloid-β) anti-Tau antibody, RNF5.We then developed hydrogel-based 2.5D model as step towards more physiologically relevant platform.Results: When compared untreated RNF5 was significantly increased (up 1.73 fold), across Transwell-based following treatment.Our results also demonstrated safety indicated by minimal changes iBEC transcriptome well little or iAstrocyte viability inflammatory responses within first 24 h post .Furthermore, successful formation our (1.4 fold) .Conclusion: Our demonstrate robust reproducible approach utilize patient screening vitro.With such platform research previously not reported, it has potential identify -deliverable drugs cell-and patient-specific , accelerating use modality AD.

Language: Английский

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Patient-Derived In Vitro Models of Microglial Function and Synaptic Engulfment in Schizophrenia

Biological Psychiatry, Journal Year: 2022, Volume and Issue: 92(6), P. 470 - 479

Published: Jan. 19, 2022

Language: Английский

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Opportunities and challenges in delivering biologics for Alzheimer’s disease by low-intensity ultrasound

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 189, P. 114517 - 114517

Published: Aug. 25, 2022

Language: Английский

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Organelle mapping in dendrites of human iPSC-derived neurons reveals dynamic functional dendritic Golgi structures

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112709 - 112709

Published: June 30, 2023

Secretory pathways within dendrites of neurons have been proposed for local transport newly synthesized proteins. However, little is known about the dynamics secretory system and whether organelles are transient or stable structures. Here, we quantify spatial dynamic behavior dendritic Golgi endosomes during differentiation human generated from induced pluripotent stem cells (iPSCs). In early neuronal development, before migration, entire apparatus transiently translocates soma into dendrites. mature neurons, elements, containing cis trans cisternae, transported along dendrites, in an actin-dependent process. Dendritic outposts display bidirectional movement. Similar structures were observed cerebral organoids. Using retention using selective hooks (RUSH) system, resident proteins efficiently endoplasmic reticulum. This study reveals dynamic, functional a map investigating dendrite trafficking neurons.

Language: Английский

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Cerebral organoids derived from patients with Alzheimer’s disease with PSEN1/2 mutations have defective tissue patterning and altered development

Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113310 - 113310

Published: Oct. 20, 2023

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study human neural development and disease. Especially in field of Alzheimer's disease (AD), remarkable effort has put into investigating molecular mechanisms behind this Then, with advent 3D neuronal cultures cerebral organoids (COs), several studies demonstrated that model can adequately mimic familial sporadic AD. Therefore, we created an AD-CO using iPSCs derived from patients AD forms explored early events progression pathogenesis. Our COs three AD-iPSC lines PSEN1(A246E) or PSEN2(N141I) mutations developed AD-specific markers vitro, yet they also uncover tissue patterning defects altered development. These findings are complemented by single-cell sequencing data confirming observation uncovering neurons AD-COs likely differentiate prematurely.

Language: Английский

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