Advances and Applications of Brain Organoids

Li, Yang; Zeng, Peng-Ming; Wu, Jian; Luo, Zhen-Ge

doi:10.1007/s12264-023-01065-2

Cited by 10 publications

(4 citation statements)

References 176 publications

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“…Ultimately, understanding complexity of nervous systems diseases and pathophysiological of human brains remain challenging despite current progress in neuroscience research. Nonetheless, a limitation barrier to apply the brain organoids as a treatment of neurodegenerative diseases resolve invasiveness in obtaining brain cells donor or human life brains and serve as one of powerful in vitro alternatives and hope to accelerate the neurodegenerative disease modeling ( Li et al, 2023 ).…”

Section: Ipsc-based Organoids Of Neurological Diseasesmentioning

confidence: 99%

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

Jusop

Thanaskody

Tye

et al. 2023

Front. Mol. Neurosci.

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Neurodegenerative diseases are adult-onset neurological conditions that are notoriously difficult to model for drug discovery and development because most models are unable to accurately recapitulate pathology in disease-relevant cells, making it extremely difficult to explore the potential mechanisms underlying neurodegenerative diseases. Therefore, alternative models of human or animal cells have been developed to bridge the gap and allow the impact of new therapeutic strategies to be anticipated more accurately by trying to mimic neuronal and glial cell interactions and many more mechanisms. In tandem with the emergence of human-induced pluripotent stem cells which were first generated in 2007, the accessibility to human-induced pluripotent stem cells (hiPSC) derived from patients can be differentiated into disease-relevant neurons, providing an unrivaled platform for in vitro modeling, drug testing, and therapeutic strategy development. The recent development of three-dimensional (3D) brain organoids derived from iPSCs as the best alternative models for the study of the pathological features of neurodegenerative diseases. This review highlights the overview of current iPSC-based disease modeling and recent advances in the development of iPSC models that incorporate neurodegenerative diseases. In addition, a summary of the existing brain organoid-based disease modeling of Alzheimer’s disease was presented. We have also discussed the current methodologies of regional specific brain organoids modeled, its potential applications, emphasizing brain organoids as a promising platform for the modeling of patient-specific diseases, the development of personalized therapies, and contributing to the design of ongoing or future clinical trials on organoid technologies.

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Section: Ipsc-based Organoids Of Neurological Diseasesmentioning

confidence: 99%

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

Jusop

Thanaskody

Tye

et al. 2023

Front. Mol. Neurosci.

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“…Moreover, such cerebral organoids have less differentiated cell types, less-developed cortical layers, and inconsistent electrical activity ( Luo et al, 2016 ; Qian et al, 2019 ; Puppo and Muotri, 2023 ). Continuous agitation within the medium via spinning bioreactors can enhance nutrient diffusion into the organoid ( Lancaster et al, 2013 ; Lancaster and Knoblich, 2014b ; Li et al, 2023 ). However, this diffusion is usually limited, and constant agitation may hamper long-term live imaging of cortical organoids.…”

Section: Introductionmentioning

confidence: 99%

Applications of multiphoton microscopy in imaging cerebral and retinal organoids

Lacin,

Yildirim

2024

Front. Neurosci.

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Cerebral organoids, self-organizing structures with increased cellular diversity and longevity, have addressed shortcomings in mimicking human brain complexity and architecture. However, imaging intact organoids poses challenges due to size, cellular density, and light-scattering properties. Traditional one-photon microscopy faces limitations in resolution and contrast, especially for deep regions. Here, we first discuss the fundamentals of multiphoton microscopy (MPM) as a promising alternative, leveraging non-linear fluorophore excitation and longer wavelengths for improved imaging of live cerebral organoids. Then, we review recent applications of MPM in studying morphogenesis and differentiation, emphasizing its potential for overcoming limitations associated with other imaging techniques. Furthermore, our paper underscores the crucial role of cerebral organoids in providing insights into human-specific neurodevelopmental processes and neurological disorders, addressing the scarcity of human brain tissue for translational neuroscience. Ultimately, we envision using multimodal multiphoton microscopy for longitudinal imaging of intact cerebral organoids, propelling advancements in our understanding of neurodevelopment and related disorders.

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“…Considering the attributes of human brain organoids 2,3 , these structures could theoretically confer advantages, such as broader and faster drug screening, expanding avenues for exploring mechanism-based drug effects, and identifying potential side effects at the cell and organ level. Their nature allows the assessment of drug compounds' impact on brain tissue, offering a platform to test candidates for neurological or psychiatric disorders 4,5 . Additionally, they can serve as tools to evaluate whether drug candidates developed for other conditions and target organs induce any adverse effects in brain tissue, especially considering the potential blood-brain barrier crossing 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Their nature allows the assessment of drug compounds' impact on brain tissue, offering a platform to test candidates for neurological or psychiatric disorders 4,5 . Additionally, they can serve as tools to evaluate whether drug candidates developed for other conditions and target organs induce any adverse effects in brain tissue, especially considering the potential blood-brain barrier crossing 5 . Presently, the primary focus lies on neurological disorders 6 and how these tools can serve as alternative instruments in drug development for such conditions.…”

Section: Introductionmentioning

confidence: 99%

Human Brain Organoids in the Preclinical Phase of Drug Development for Migraine

Gazerani

2024

MRAJ

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Developing drugs for brain disorders poses significant hurdles. These challenges stem from the scarcity of optimal models for preclinical drug testing and the often observed lack of translation from preclinical to human clinical trials. Further complexity arises from the specific targeting required in many brain disorders, with drug delivery often impeded by the necessity to cross the blood-brain barrier (BBB). As such, the search for novel and efficient platforms for preclinical drug development is a vibrant area of research. In acknowledgment of the limitations of animal tests - such as the lack of translation owing to species differences - and in alignment with the principles of reduction, refinement, and replacement (3Rs), the scientific community is moving towards promoting animal-free drug development plans. In this context, human brain organoids are rapidly emerging as potential alternatives to traditional methods. These early-stage in vitro models, mirroring in vivo complexities, hold great promise for preclinical drug testing for brain disorders. Stable organoid phenotypes and the uncovering of disease-specific features could soon elevate them to a valuable strategy in pharmaceutical testing for a range of brain disorders. Recent advancements in assay-ready organoid platforms and microfluidic chips present considerable potential for the application of human brain organoids in drug development. This commentary briefly discusses the generation of human brain organoids and their application in drug development with existing examples, focusing on their potential use in preclinical drug development for migraine, a prevalent, complex, and disabling brain disorder. The associated challenges and opportunities will also be outlined.

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Advances and Applications of Brain Organoids

Cited by 10 publications

References 176 publications

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

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

Applications of multiphoton microscopy in imaging cerebral and retinal organoids

Human Brain Organoids in the Preclinical Phase of Drug Development for Migraine

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