Assembloid models of cell-cell interaction to study tissue and disease biology

Cell stem cell, Год журнала: 2024, Номер 31(11), С. 1563 - 1573

Опубликована: Окт. 24, 2024

Язык: Английский

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Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids

Cell stem cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Organoid bioprinting: from cells to functional tissues

Nature Reviews Bioengineering, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Язык: Английский

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Assembloid model to study loop circuits of the human nervous system

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 14, 2024

Abstract Neural circuits connecting the cerebral cortex, basal ganglia and thalamus are fundamental networks for sensorimotor processing their dysfunction has been consistently implicated in neuropsychiatric disorders 1-9 . These recursive, loop have investigated animal models by clinical neuroimaging, however, direct functional access to developing human neurons forming these limited. Here, we use pluripotent stem cells reconstruct an vitro cortico-striatal-thalamic-cortical circuit creating a four-part assembloid. More specifically, generate regionalized neural organoids that resemble key elements of circuit, functionally integrate them into assembloids using custom 3D-printed biocompatible wells. Volumetric mesoscale calcium imaging, as well extracellular recordings from individual parts reveal emergence synchronized patterns neuronal activity. In addition, multi–step rabies retrograde tracing approach demonstrate formation connectivity across network assembloids. Lastly, apply this system study heterozygous loss ASH1L gene associated with autism spectrum disorder Tourette syndrome discover aberrant activity disease model Taken together, multi-cellular platform will facilitate investigations context early development conditions.

Язык: Английский

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Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders

Frontiers in Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Янв. 8, 2025

Neurodevelopmental disorders (NDDs) affect 4.7% of the global population and are associated with delays in brain development a spectrum impairments that can lead to lifelong disability even mortality. Identification biomarkers for accurate diagnosis medications effective treatment lacking, part due historical use preclinical model systems do not translate well clinic neurological disorders, such as rodents heterologous cell lines. Human-induced pluripotent stem cells (hiPSCs) promising vitro system modeling NDDs, providing opportunities understand mechanisms driving NDDs human neurons. Functional assays, including patch clamping, multielectrode array, imaging-based popular tools employed hiPSC disease models investigation. Recent progress machine learning (ML) algorithms also presents unprecedented advance NDD research process. In this review, we compare two-dimensional three-dimensional formats modeling, discuss applications functional offer insights on incorporating ML into hiPSC-based drug screening.

Язык: Английский

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Emerging approaches to enhance human brain organoid physiology

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.

Язык: Английский

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Protocol for generating human assembloids to investigate thalamocortical and corticothalamic synaptic transmission and plasticity

STAR Protocols, Год журнала: 2025, Номер 6(1), С. 103630 - 103630

Опубликована: Фев. 7, 2025

Язык: Английский

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Modeling forebrain regional development and connectivity by human brain organoids

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 91, С. 102324 - 102324

Опубликована: Фев. 20, 2025

Язык: Английский

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Exploring human brain development and disease using assembloids

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Brain Organoids and Assembloids—From Disease Modeling to Drug Discovery

Cells, Год журнала: 2025, Номер 14(11), С. 842 - 842

Опубликована: Июнь 4, 2025

Brain organoids are self-organized, three-dimensional (3D) aggregates derived from human embryonic stem cells, induced pluripotent or primary organs with cell types and cellular architectures resembling those of the developing brain. Recent studies have shown use region-specific brain for modeling various diseases ranging neurodevelopmental neurodegenerative to different cancers, which numerous applications in fundamental research development new drugs, personalized treatment, regenerative medicine. Consequently, drug discovery is complex challenging still an emerging area this field. This review article summarizes cells used organoid generation, organoids, functional assays their characterization. In addition, we discuss pediatric as well application assembloids, tumoroids cancer neuroscience. We further explore recent advances using high-throughput screening improve discovery.

Язык: Английский

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