The emerging technology of brain organoids deriving from human pluripotent stem cells provides unprecedented opportunities to study human brain development and associated disorders. Various brain organoid protocols have been developed that can recapitulate some key features of cell type diversity, cytoarchitectural organization, developmental processes, functions, and pathologies of the developing human brain. In this review, we focus on patterning of human stem cell-derived brain organoids. We start with an overview of general procedures to generate brain organoids. We then highlight some recently developed brain organoid protocols and chemical cues involved in modeling development of specific human brain regions, subregions, and multiple regions together. We also discuss limitations and potential future improvements of human brain organoid technology.
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http://dx.doi.org/10.1016/j.conb.2022.102536 | DOI Listing |
Cell Regen
January 2025
Department of Neurology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
The cultivation and differentiation of human embryonic stem cells (hESCs) into organoids are crucial for advancing of new drug development and personalized cell therapies. Despite establishing of chemically defined hESC culture media over the past decade, these media's reliance on growth factors, which are costly and prone to degradation, poses a challenge for sustained and stable cell culture. Here, we introduce an hESC culture system(E6Bs) that facilitates the long-term, genetically stable expansion of hESCs, enabling cells to consistently sustain high levels of pluripotency markers, including NANOG, SOX2, TRA-1-60, and SSEA4, across extended periods.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology.
View Article and Find Full Text PDFBrain Inform
January 2025
Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY, 10032, USA.
Calcium plays an important role in regulating various neuronal activities in human brains. Investigating the dynamics of the calcium level in neurons is essential not just for understanding the pathophysiology of neuropsychiatric disorders but also as a quantitative gauge to evaluate the influence of drugs on neuron activities. Accessing human brain tissue to study neuron activities has historically been challenging due to ethical concerns.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Korea.
Human cerebral organoids serve as a quintessential model for deciphering the complexities of brain development in a three-dimensional milieu. However, imaging these organoids, particularly when they exceed several millimeters in size, has been curtailed by the technical impediments such as phototoxicity, slow imaging speeds, and inadequate resolution and imaging depth. Addressing these pivotal challenges, our study has pioneered a high-speed scanning microscope, synergistically coupled with advanced computational image processing.
View Article and Find Full Text PDFTrends Cell Biol
January 2025
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Electronic address:
Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, and in vivo resemblance, current efforts are directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches and their latest developments are discussed, including stem cell optimization, refining morphogen administration strategies, altering the extracellular matrix (ECM) niche, and manipulating tissue architecture to mimic in vivo brain morphogenesis.
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