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Whole-brain Organoid
Overview of Whole-brain Organoid
For decades, most of our understanding of brain development and diseases affecting the central nervous system (CNS) has been based on traditional two-dimensional cell cultures and animal models. While many experimental methods rely on rodents or non-human primates, the brains of these animals differ substantially from those of humans in terms of both their structure and function. For example, the human brain contains a human-exclusive outward-expanded subventricular zone (oSVZ) that increases the volume and function of the mature cerebrum. Anthropological studies have revealed that the human brain contains more elaborate cytoarchitectonic subdivisions than the brains of lissencephalic primates and gyrencephalic rodents. Besides, animal brains exhibit a lower encephalization quotient, lower neuronal density, and distinct permutation characteristic when compared with those of humans. Therefore, preclinical experiments using conventional models sometimes lead to disappointing results in disease modeling and drug screening studies.
Three-dimensional cerebral organoids form more heterogeneous structures in vitro, eventually developing into different progenitor zones and taking on the characteristics of various brain regions. Since these systems more closely mirror the spatial architecture of the brain in vivo, they can be used to study pathophysiological processes as well as the effects of genetic manipulation on such processes.
Fig.1 Schematic diagram representing cerebral organoid generation from human induced pluripotent stem cells (hiPSCs).1
Services at Creative Biolabs
Creative Biolabs has been focusing on neuroscience for years. Our scientists have never stopped pursuing the frontier of neuroscience and we throw our attention on in vitro models. With strong foundations and an excellent specialist team, we have developed a comprehensive custom brain organoid platform. If you are interested in custom whole-brain organoid services, or any other custom brain organoid services, please feel free to contact us for more information.
We offer a state-of-the-art whole-brain organoid development service. This service is for academic, industrial, and pharmaceutical research groups that need a reliable, reproducible, and robust process to model human brain development and disease in vitro. Please note that this is designed strictly for research purposes and not for therapeutic use or clinical applications.
- We employ advanced procedures to differentiate the iPSCs derived neurons into brain organoids that reproduce key features of whole-brain development, including regional specialization, neuron types and subtypes, neurogenesis, and neuron maturation.
- We harness cutting-edge techniques such as cerebral organoid technology to generate a 3D model mimicking the complex layers and structure of the human brain. Our organoids include diverse cell types that replicate different regions of the brain, including forebrain, hindbrain, and midbrain.
- We utilize state-of-the-art imaging systems to monitor the growth and organogenesis of the organoids, and comprehensive analysis tools to verify their cellular composition and structure.
The overarching aim of our whole-brain organoid development service is to facilitate your research by offering an ex vivo system that closely recapitulates the in vivo human brain, overcoming the limitations of traditional 2D cell culture and animal models in neuroscience and neurology research. We also offer flexibility in our services, including but not limited to:
| Services | Descriptions |
|---|---|
| Custom CNS Disease Modeling | Our platform can offer reliable custom CNS disease modeling services including but not limited to Alzheimer's disease models, Huntington's disease models, and Parkinson's disease models. |
| Neurotoxicity Screening | We can provide a novel neurotoxicity screening service for the discovery of CNS drugs. We have a series of iPSC-derived neuronal lineage cells for your projects, and we can also reprogram and differentiate iPSC cells from your samples. |
| STEMOD™ Advanced Drug Discovery | Our platform has advanced neuroscience ex vivo models, neuroscience assay techniques, and neuroscience research tools. These technologies will cover every important stage of CNS drug discovery, resulting in a one-stop shop for our customers. |
Published Data
Ramani, Anand, et al. established a scalable approach to generating whole-brain organoids with reproducible quality and quantity, capable of modeling diseases and screening drugs. They described a simplified culture method for inducing direct differentiation of iPSC into neuroepithelium, omitting EB and using an extracellular matrix. Their method produces a large number of brain organoids (Hi-Q brain organoids). Hi-Q brain organoids exhibit similar cellular diversity, cytoarchitecture, maturation time, and function.
Fig. 2 Generation of Hi-Q brain organoids.2
Applications of Whole-brain Organoid in Research
Neuropsychiatric diseases such as schizophrenia, depression, and autism spectrum disorder (ASD) have complex disease profiles, affecting multiple aspects of cognition, personality, and perception. Due to such complexities in symptomatology, polygenetic etiology, and the limited availability of diagnostic markers/research models, neuropsychiatric diseases, which are now considered neurodevelopmental in origin, have been difficult to study experimentally and remain poorly understood.
- Schizophrenia and ASD
- Miller-Dieker syndrome (MDS)
Cerebral organoids have become a new avenue for modeling developmental abnormalities and genetic alterations associated with neuropsychiatric disease. Indeed, such models have been used to uncover the cellular phenotypes and pathophysiological mechanisms underlying disorders such as schizophrenia and ASD. Yoon et al. used hiPSC-derived cortical neural rosettes to study the molecular mechanisms underlying schizophrenia, observing that 15q11.2 haploinsufficiency leads to NSC deficits associated with adherens junctions. The authors further noted that CYFIP1 and WAVE signaling plays an important role in generating schizophrenia phenotypes.
Miller-Dieker syndrome (MDS) is another severe neurodevelopmental disease with dramatic cortical malformation. Reduced neuroepithelial loops have been developed in cerebral organoids generated from MDS patients, with smaller sizes compared with control organoids. Studies using telencephalic organoids derived from hiPS cells of MDS patients found evidence of prolonged mitosis of outer radial glia cells, increased apoptosis of neuroepithelial stem cells, and increased vertical spindle orientation. Researchers using cerebral organoids to explore the mechanism of Sandhoff disease found accumulated GM2 ganglioside and impaired neuronal differentiation altered by the disease process.
These studies demonstrated that cerebral organoids can be broadly used to unravel the pathogenic cellular mechanisms of neurodevelopmental diseases.
Key Points:
- Cerebral organoids can be used to model neurodevelopmental and infectious diseases.
- Cerebral organoids are superior to traditional neuroepithelium methods.
- Cerebral organoid methods require more specialized and complex culture conditions.
- Cerebral organoid is a powerful tool in CNS diseases research.
FAQs
Q: What kind of scientific experiments can these organoids be used for?
A: These organoids can be used for a vast array of experiments like studying neurodevelopmental disorders, neurodegenerative diseases, drug testing, and studying the molecular and cellular mechanics of the brain. Their complex structure and functionality provide a powerful model for in-depth biological investigations. They can also be altered genetically to represent different diseases, opening new areas for novel therapeutic strategies.
Q: How similar are these organoids to real brain tissue?
A: While these organoids cannot completely replicate the complexity of the human brain, they recapitulate key aspects of brain development and function. They contain various types of neurons and glia in specific layers, resembling the architecture of a developing brain.
Q: What support do you provide after delivering the organoids?
A: We offer comprehensive post-delivery support, including detailed protocols for maintaining and experimenting with the organoids, troubleshooting assistance, and ongoing technical support. Our team is available to help you optimize your experiments and ensure that you achieve reliable and reproducible results with our brain organoids. Our commitment is to ensure that your research progresses smoothly and successfully.
Q: What makes your service different from others?
A: Our service stands out due to our commitment to customization, quality, and support. We tailor the organoid development process to meet specific research needs, ensuring high relevance and utility. Our rigorous quality control guarantees consistent and reliable organoids. Additionally, our comprehensive post-delivery support helps researchers maximize the potential of our organoids in their experiments.
Scientific Resources
References
- Liu, F., et al. Advances in Cerebral Organoid Systems and their Application in Disease Modeling. Neuroscience. 2019, 399: 28-38.
- Ramani, Anand, et al. "Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening." bioRxiv (2023): 2023-10.
For Research Use Only. Not For Clinical Use.