Assessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoids

Cvetkovic, Caroline; Patel, Rajan; Shetty, Arya; Hogan, Matthew K.; Anderson, Morgan; Basu, Nupur; Aghlara-Fotovat, Samira; Ramesh, Srivathsan; Sardar, Debosmita; Veiseh, Omid; Ward, Michael E.; Deneen, Benjamin; Horner, Philip J.; Krencik, Robert

doi:10.1083/jcb.202107135

Cited by 14 publications

(11 citation statements)

References 75 publications

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“…The study of human reactive astrocytes has, therefore, been limited by the availability of resources and, more importantly, because there are important transcriptional and functional differences between rodent and human astrocytes [ 127 , 210 ]. In a recent study, Cvetkovic et al address this technical shortcoming by developing bio-engineered neural organoid cultures containing mature astrocytes which allow for the investigation of the dynamics of astrocyte reactivity and its downstream effects on neuronal activity [ 211 , 212 ]. The authors successfully generated multicellular organoid systems containing astrocytes that exhibited key features of mature cells.…”

Section: The Versatility Of 3d Brain Organoids: Modeling Neurodevelop...mentioning

confidence: 99%

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

D’Antoni,

Mautone,

Sanchini

et al. 2023

IJMS

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

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Section: The Versatility Of 3d Brain Organoids: Modeling Neurodevelop...mentioning

confidence: 99%

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

D’Antoni,

Mautone,

Sanchini

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…A Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified TNF signalling, IL-17 signalling, MAPK signalling, Kaposi sarcoma-associated herpesvirus infection, and NF-κB signalling as the top five significantly upregulated pathways. This tool allowed for the direct activation of astrocytes in neural organoids and offers an opportunity for further studies of astrocyte reactivity in a 3D culture system [ 126 ].…”

Section: Complex 2d Ipsc Culture Modelsmentioning

confidence: 99%

Human iPSC-derived glia models for the study of neuroinflammation

Stöberl,

Maguire,

Salis

et al. 2023

J Neuroinflammation

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Neuroinflammation is a complex biological process that plays a significant role in various brain disorders. Microglia and astrocytes are the key cell types involved in inflammatory responses in the central nervous system. Neuroinflammation results in increased levels of secreted inflammatory factors, such as cytokines, chemokines, and reactive oxygen species. To model neuroinflammation in vitro, various human induced pluripotent stem cell (iPSC)-based models have been utilized, including monocultures, transfer of conditioned media between cell types, co-culturing multiple cell types, neural organoids, and xenotransplantation of cells into the mouse brain. To induce neuroinflammatory responses in vitro, several stimuli have been established that can induce responses in either microglia, astrocytes, or both. Here, we describe and critically evaluate the different types of iPSC models that can be used to study neuroinflammation and highlight how neuroinflammation has been induced and measured in these cultures.

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“…In addition to modeling AD, cerebral organoids and chip‐based models have been used for drug delivery, efficacy testing, and toxicity assessments for several cognitive diseases 62–65 . For example, Groveman et al created an iPSC‐derived cerebral organoid to model Creutzfeldt–Jakob disease (CJD) as a drug testing platform.…”

Section: Model Systems For Admentioning

confidence: 99%

“…61 In addition to modeling AD, cerebral organoids and chip-based models have been used for drug delivery, efficacy testing, and toxicity assessments for several cognitive diseases. [62][63][64][65] For example, Grove- gene expression, therefore, demonstrating a higher level of standardization and introducing less bias for drug screening. 64 Cerebral organoid models offer advantages over animal models and 2D cultures in modeling AD (Figure 3d).…”

Section: D Culture Modelsmentioning

confidence: 99%

Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms

Sreenivasamurthy

Laul

Kim

et al. 2022

Bioengineering & Transla Med

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Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two-dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain-specific tissue structure, function, and cellular diversity. Recently, the emergence of three-dimensional (3D) cerebral organoids using tissue engineering and induced pluripotent stem cell technology has paved the way to develop models that resemble features of human brain tissue more accurately in comparison to prior models. In this review, we focus on summarizing key research strategies for engineering in vitro 3D human brain-specific models, major discoveries from using AD cerebral organoids, and its future perspectives.

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Assessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoids

Cited by 14 publications

References 75 publications

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

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

Human iPSC-derived glia models for the study of neuroinflammation

Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms

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