Engineering brain assembloids to interrogate human neural circuits

Miura, Yuki; Li, Min-Yin; Revah, Omer; Yoon, Se-Jin; Narazaki, Genta; Paşca, Sergiu P.

doi:10.1038/s41596-021-00632-z

Cited by 81 publications

(84 citation statements)

References 32 publications

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“…Human induced pluripotent stem (hiPS) cell lines were validated using standardized methods as described previously 9, 18 . Cultures were tested for and maintained Mycoplasma free.…”

Section: Methodsmentioning

confidence: 99%

Biocompatible polymers for scalable production of human neural organoids

Narazaki

Miura

Pavlov

et al. 2022

Preprint

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The generation of neural organoids from human pluripotent stem cells holds great promise in modeling disease and screenings drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here, we develop a scalable neural organoid platform by screening biocompatible polymers that prevent fusion of organoids cultured in suspension. We show that addition of one inexpensive polysaccharide enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids.

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“…Human induced pluripotent stem (hiPS) cell lines were validated using standardized methods as described previously 9, 18 . Cultures were tested for and maintained Mycoplasma free.…”

Section: Methodsmentioning

confidence: 99%

Biocompatible polymers for scalable production of human neural organoids

Narazaki

Miura

Pavlov

et al. 2022

Preprint

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“…Markedly, brain-region specific organoid systems don’t offer the opportunity to model multiple regions and interactions between them. To address this, different brain-region organoids have been co-cultured or fused together in “assembloid” approaches ( Bagley et al, 2017 ; Birey et al, 2017 ; Xiang et al, 2017 ; Sloan et al, 2018 ; Xiang et al, 2019 ; Miura et al, 2022 ). This can be achieved via several methods, including stepwise assembly of already formed organoids according to neurodevelopmental trajectory, or spontaneous fusion on a shaker.…”

Section: Enhancing Organoid Cultures With Bioelectricitymentioning

confidence: 99%

“…This can be achieved via several methods, including stepwise assembly of already formed organoids according to neurodevelopmental trajectory, or spontaneous fusion on a shaker. The fused organoids are demonstrated to functionally integrate and have transcriptomes representative of the foetal brain ( Xiang et al, 2017 ; Miura et al, 2022 ). Application of exogenous EFs during the assembly process could enhance migratory behaviour between regions and promote regional fate determination.…”

Section: Enhancing Organoid Cultures With Bioelectricitymentioning

confidence: 99%

“…Therefore, as we look towards next-generation organoids, culture conditions must be optimised to address these shortcomings. Currently, headway is being made through fine-tuning of bioengineering approaches, such as 3D biomaterial compositions to support structural development, assembloid technology to generate wider CNS structures, or organ-on-a-chip technology to promote oxygenation ( Achberger et al, 2019 ; Bierman-Duquette et al, 2021 ; Ao et al, 2022 ; Miura et al, 2022 ). However, to best replicate organogenesis in vitro , understanding native mechanisms in basic development is crucial.…”

Section: Introductionmentioning

confidence: 99%

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Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System

O’Hara-Wright

Mobini

Gonzalez‐Cordero

2022

Front. Cell Dev. Biol.

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Pluripotent stem cell-derived organoid models of the central nervous system represent one of the most exciting areas in in vitro tissue engineering. Classically, organoids of the brain, retina and spinal cord have been generated via recapitulation of in vivo developmental cues, including biochemical and biomechanical. However, a lesser studied cue, bioelectricity, has been shown to regulate central nervous system development and function. In particular, electrical stimulation of neural cells has generated some important phenotypes relating to development and differentiation. Emerging techniques in bioengineering and biomaterials utilise electrical stimulation using conductive polymers. However, state-of-the-art pluripotent stem cell technology has not yet merged with this exciting area of bioelectricity. Here, we discuss recent findings in the field of bioelectricity relating to the central nervous system, possible mechanisms, and how electrical stimulation may be utilised as a novel technique to engineer “next-generation” organoids.

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“…The high number of cells needed can limit their practical use for the screening of large collection of compounds. In these neural models, the formation of a connected, functional neuronal network is achieved by proximity effects, and long-distance connections are now being developed by forming the so-called assembloid structures [15,16], in which organoids or spheroids mimicking different regions of the brains are connected by contact fusion. The cellular and synaptic plasticity of such systems allows for neuronal extensions to form functional connections between the fused organoids or spheroids of an assembloid.…”

Section: Introductionmentioning

confidence: 99%

High throughput 3D gel-based neural organotypic model for cellular assays with fluorescence biosensors

Kundu¹,

Boutin

Strong

et al. 2022

Preprint

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Three-dimensional (3D) organotypic models that capture native-like physiological features of tissues are being pursued as clinically predictive assays for therapeutics development. A range of 3D neural organotypic models are being developed to mimic brain morphology, physiology, and pathology of neurological disease. Biofabrication of 3D gel-based cellular systems is emerging as a versatile technology to produce spatially and cell-type tailored, physiologically complex and native-like tissue models. Here we produce 3D fibrin gel-based functional neural co-culture models with human iPSC differentiated dopaminergic or glutamatergic neurons and astrocytes. We further introduce genetically encoded fluorescence biosensors for real time functional measurements of intracellular calcium and levels of dopamine and glutamate neurotransmitters, in a high throughput compatible plate format. We use optogenetic activation and pharmacological perturbations to demonstrate that functional responses in 3D fibrin gel neural models are as relevant to be expected from in vivo data, compared to the equivalent 2D neural models.

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Engineering brain assembloids to interrogate human neural circuits

Cited by 81 publications

References 32 publications

Biocompatible polymers for scalable production of human neural organoids

Biocompatible polymers for scalable production of human neural organoids

Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System

High throughput 3D gel-based neural organotypic model for cellular assays with fluorescence biosensors

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