Brain Organoids: A Game-Changer for Drug Testing

Giorgi, Chiara; Lombardozzi, Giorgia; Ammannito, Fabrizio; Scenna, Marta Sofia; Maceroni, Eleonora; Quintiliani, Massimiliano; d’Angelo, Michele; Cimini, Annamaria; Castelli, Vanessa

doi:10.3390/pharmaceutics16040443

Cited by 3 publications

(4 citation statements)

References 103 publications

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“…This document was created to provide a basic guide for more effective testing. In this document, we describe the characteristics of whole-brain organoids and the following region-specific brain organoids: ( 1 ) dorsal forebrain, ( 2 ) ventral forebrain, ( 3 ) hypothalamus, ( 4 ) pituitary gland, ( 5 ) midbrain, ( 6 ) cerebellum, and ( 7 ) spinal cord.…”

Section: Considerations and Scopementioning

confidence: 99%

“…As a technique for modeling the complex characteristics of the central nervous system (CNS) ex vivo , brain/neural organoids are characterized by their ability to reproduce nervous system development, and the complex structure and electrophysiology of neuronal networks, while simultaneously reflecting interactions between different cell types and various microenvironmental factors. As such, by using brain/neural organoid techniques to create a model with the highest similarity to real human tissue, it is possible to overcome the limitations of conventional two-dimensional cell culture models and to perform high-caliber disease model research ( 3 - 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Guidelines for Manufacturing and Application of Organoids: Brain

Kwak,

Park,

Lee

et al. 2024

Int J Stem Cells

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This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.

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Section: Considerations and Scopementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Guidelines for Manufacturing and Application of Organoids: Brain

Kwak,

Park,

Lee

et al. 2024

Int J Stem Cells

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“…Neuronal organoids are highly valuable tools for studying the brain because they can replicate various brain regions capable of interacting with each other or develop to resemble specific brain sections [ 206 ]. Despite variability among different brain organoids, they contain the same cell types found in the human brain.…”

Section: Future Perspectivesmentioning

confidence: 99%

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

Pagotto,

Santos,

Osman

et al. 2024

Antioxidants

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Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

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“…The range of their applications is broad, including neurobiological basic research, drug discovery, gene therapy, cell therapy, precision and regenerative medicine ( Park et al, 2021 ; Zhao et al, 2022 ; Kim and Chang, 2023 ; Giorgi et al, 2024 ).…”

Section: Introductionmentioning

confidence: 99%

Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive

Urrestizala-Arenaza,

Cerchio,

Cavaliere

et al. 2024

Front. Cell. Neurosci.

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In 2013, M. Lancaster described the first protocol to obtain human brain organoids. These organoids, usually generated from human-induced pluripotent stem cells, can mimic the three-dimensional structure of the human brain. While they recapitulate the salient developmental stages of the human brain, their use to investigate the onset and mechanisms of neurodegenerative diseases still faces crucial limitations. In this review, we aim to highlight these limitations, which hinder brain organoids from becoming reliable models to study neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Specifically, we will describe structural and biological impediments, including the lack of an aging footprint, angiogenesis, myelination, and the inclusion of functional and immunocompetent microglia—all important factors in the onset of neurodegeneration in AD, PD, and ALS. Additionally, we will discuss technical limitations for monitoring the microanatomy and electrophysiology of these organoids. In parallel, we will propose solutions to overcome the current limitations, thereby making human brain organoids a more reliable tool to model neurodegeneration.

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Brain Organoids: A Game-Changer for Drug Testing

Cited by 3 publications

References 103 publications

Guidelines for Manufacturing and Application of Organoids: Brain

Guidelines for Manufacturing and Application of Organoids: Brain

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive

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