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The potential of brain organoids in addressing the heterogeneity of synucleinopathies.
Synucleinopathies are a group of diseases characterized by neuronal and glial accumulation of α-synuclein (aSyn) linked with different clinical presentations, including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Dementia with Lewy Bodies (DLB) and Multiple system atrophy (MSA). Interestingly, the structure of the aSyn aggregates can vary across different synucleinopathies. Currently, it is unclear how the aSyn protein can aggregate into diverse structures and affect distinct cell types and various brain regions, leading to different clinical symptoms. Recent advances in induced pluripotent stem cells (iPSCs)-based brain organoids (BOs) technology provide an unprecedented opportunity to define the etiology of synucleinopathies in human brain cells within their three-dimensional (3D) context. In this review, we will summarize current advances in investigating the mechanisms of synucleinopathies using BOs and discuss the scope of this platform to define mechanisms underlining the selective vulnerability of cell types and brain regions in synucleinopathies.
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Research progress of brain organoids in the field of diabetes.
Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.
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Matisse and the Organoids: The Art of Science.
Over the past few decades, scientists have transformed the way they do and understand science. They are now exploring their more creative side. This approach has accelerated fascinating discoveries such as human induced pluripotent stem cells and brain organoids; however, they have not been able to jump over the communication barrier with society. La Danse des Astrocytes, a scene observed during a routine microscopy session working on midbrain organoids, has motivated this essay, which urges scientists to find new forms of science communication and to work as a community to achieve the consolidation of a scientific culture.
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Brain organoids: A new frontier of human neuroscience research.
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Human iPSC-Derived Brain Organoids: A Disease-Oriented Evaluation of Modeling Fidelity.
Two-dimensional (2D) cell culture systems and conventional animal models have been crucial in the study of central nervous system (CNS) pathology. However, they are limited in their abilities to elucidate human-specific neurobiology and disease etiology. Human induced pluripotent stem cell (iPSC)-derived brain organoids have emerged as a complementary platform that offers a three-dimensional (3D) structure and human-specific environment. They exhibit cellular heterogeneity, apical-basal polarity, and the ability to perform tissue-specific functions such as absorption, secretion, and electrophysiological activity. This review critically evaluates the use of iPSC-derived brain organoids as a disease-focused approach to study neuroinflammation, neurodegeneration, infection, and aging. Organoids provide a model for early pathogenic events, cellular interactions, and human-specific responses, providing insights into disease hallmarks such as tau and amyloid pathology, the vulnerability of dopaminergic neurons, and host-pathogen interactions. However, they are limited by developmental immaturity, inadequate systemic integration, and heterogeneity across models, which hinders their ability to represent late-stage disease progression and human level physiology. Therefore, their primary use lies in modeling human-specific early disease mechanisms, while integration with animal models and in vitro systems is crucial for progressing translational neuroscience.
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A Simple Method of Generating 3D Brain Organoids Using Standard Laboratory Equipment.
3D brain organoids are a powerful tool with prospective application for the study of neural development and disease. Here we describe the growth factor-free method of generating cerebral organoids from feeder-dependent or feeder-free human pluripotent stem cells using standard laboratory equipment. The protocol outlined below allows generation of 3D tissues, which replicate human early in vivo brain development up to the end of the first trimester, both in terms of morphology and gene expression pattern.
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Brain organoids: a next step for humanized Alzheimer's disease models?
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A home for brain organoids.
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How cerebral organoids are guiding brain-cancer research and therapies.
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Intermittent Propofol Exposure Induces Neurodevelopmental Alterations in Human Brain Organoids.
The administration of anaesthesia during pregnancy may have implications for fetal brain development. This study used H1 embryonic stem cell-derived human brain organoids (HBOs) to investigate effects of intermittent propofol exposure (IPE). HBOs were subjected to early IPE from 47 to 50 days in vitro (div), or late IPE from 77 to 80 div, using a clinically supra-anaesthetic concentration of 50 µM propofol. This was followed by cultivation without propofol for an additional 10 div, and HBOs were subsequently analysed at 60 or 90 div. Determination of HBO growth and lactate release did not provide evidence of neurotoxicity. Multi-electrode array recordings indicated an increased neuronal activity at 60 div following early IPE, an effect not observed at 90 div following late IPE. RNA-sequencing revealed that IPE up-regulated genes associated with neurodevelopment and synapse functions at 60 div, which overlapped with naturally up-regulated genes during HBO development from 60 to 90 div. These findings indicate that early IPE accelerates brain maturation in HBOs, suggesting possible deviations from the normal developmental trajectory in the fetal brain.