Applications of brain organoids in neurodevelopment and neurological diseases

Sun, Nan; Meng, Xiangqi; Liu, Yuxiang; Song, Dan; Jiang, Chuanlu; Cai, Jinquan

doi:10.1186/s12929-021-00728-4

Cited by 55 publications

(40 citation statements)

References 132 publications

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“…Human cerebral organoids have recently emerged as a state-of-the-art technology for modeling human brain development in three-dimensions (3D). This may eventually represent an alternative strategy for the better recapitulation of human brain aging in vitro [ 323 ]. In summary, there is currently great interest in determining the extent to which various available strategies can be combined in order to provide a more complete picture of actual cellular senescence in human neurons ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

et al. 2021

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With an increased life expectancy among humans, aging has recently emerged as a major focus in biomedical research. The lack of in vitro aging models—especially for neurological disorders, where access to human brain tissues is limited—has hampered the progress in studies on human brain aging and various age-associated neurodegenerative diseases at the cellular and molecular level. In this review, we provide an overview of age-related changes in the transcriptome, in signaling pathways, and in relation to epigenetic factors that occur in senescent neurons. Moreover, we explore the current cell models used to study neuronal aging in vitro, including immortalized cell lines, primary neuronal culture, neurons directly converted from fibroblasts (Fib-iNs), and iPSC-derived neurons (iPSC-iNs); we also discuss the advantages and limitations of these models. In addition, the key phenotypes associated with cellular senescence that have been observed by these models are compared. Finally, we focus on the potential of combining human iPSC-iNs with genome editing technology in order to further our understanding of brain aging and neurodegenerative diseases, and discuss the future directions and challenges in the field.

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Section: Discussionmentioning

confidence: 99%

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

et al. 2021

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“…Brain organoids have validated their value as a model for the human brain, even though it is still difficult to fully recapitulate the real human brain. First, the cell-type diversity needs further expansion in brain organoids ( Sun et al, 2021 ). Although protocols have been established to enrich neuronal cell types in brain organoids, including non-neuronal lineage cells such as endothelial cells and microglial cells ( Abud et al, 2017 ; Cakir et al, 2019 ; Ham et al, 2020 ; Shi et al, 2020 ), it is still difficult to establish the immune environment in brain organoids.…”

Section: Further Directionsmentioning

confidence: 99%

The Application of Brain Organoids in Assessing Neural Toxicity

Fan

Wang

et al. 2022

Front. Mol. Neurosci.

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The human brain is a complicated and precisely organized organ. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect the biological processes of the brain or its function and eventually lead to neurological diseases. Animal models may not fully recapitulate the human brain for testing neural toxicity. Brain organoids with self-assembled three-dimensional (3D) structures provide opportunities to generate relevant tests or predictions of human neurotoxicity. In this study, we reviewed recent advances in brain organoid techniques and their application in assessing neural toxicants. We hope this review provides new insights for further progress in brain organoid application in the screening studies of neural toxicants.

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“…The development of the brain organoid is another crucial achievement in the arena of organoid technology. This not only is helpful in the modeling of several neuropsychiatric, neurodegenerative brain disorders, developmental disorders, neurotropic infectious diseases, and tumors but also serves as an efficient model for toxicological assessment of several drugs, precisely those which can surmount the blood–brain barrier ( Di Lullo and Kriegstein, 2017 ; Chuye et al, 2018 ; Chen et al, 2020 ; Shou et al, 2020 ; Velasco et al, 2020; Sun et al, 2021 ). The brain organoid model has a definitive advantage over cell culture-based studies as the organoid can act as a direct source in terms of targeted species and personalization, heterogeneity, and interaction analysis ( Qian et al, 2018 ).…”

Section: Brain Organoidsmentioning

confidence: 99%

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Prasad

Kumar

Buragohain

et al. 2021

Front. Cell Dev. Biol.

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Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.

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Applications of brain organoids in neurodevelopment and neurological diseases

Cited by 55 publications

References 132 publications

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

The Application of Brain Organoids in Assessing Neural Toxicity

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

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