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Cerebellar Organoid
Introduction to Cerebellar Organoids
The cerebellum plays an important role in maintaining balance and movement coordination. Some studies showed that the functional defects of different cerebellar neurons may result in cerebellar dysfunction. In the past decades, postmortem tissues are major source for research of disease-related neuronal phenotypes. Subsequently, immortalized cell lines, as well as rodent animal models, have been used in neurodegenerative diseases study. In recent years, human induced pluripotent stem cells (iPSCs) present great potentials for disease modeling, the cerebral organoids generated from patients' iPSCs are beneficial for the proposal of treatment strategies.
Studies have shown that the maturation of cerebellar neurons requires isolation of organoids, sorting of cerebellar progenitor cells, and co-culture with feeder cells in a monolayer culture system. Protein analysis can be used to detect different cerebellar cell populations, and immunostaining of organoid slices can further evaluate the spatial organization of specific cerebellar cell populations.
Fig.1 Efficient cerebellar differentiation and maturation in human iPSC-derived organoids.1
3D Cerebellar Organoid Culture System
Creative Biolabs has developed a dynamic 3D culture system to produce cerebellar organoids based on iPSCs. It is a single-use vertical wheel bioreactor equipped with a large vertical impeller to provide optimal culture conditions. During the maturation process, different types of cerebellar neurons can be observed, such as Purkinje cells, granule cells, Golgi cells, unipolar brush cells, as well as deep cerebellar nuclei projection neurons. After 35 days, these neurons can survive for almost 90 days for disease modeling use.
Our Cerebellar Organoid Development Service
Our cerebellar organoid development service offers solutions for understanding the biology of the human cerebellum, a complex brain structure. The service assists researchers in exploring brain development, diseases, and potential therapeutic applications that involve the cerebellum. Our service essentially involves the growth of 3D cerebellar organoids from pluripotent stem cells under controlled laboratory conditions.
What We Do
- Cerebellar Organoid Culture
- Customization - This could include the development of organoids with specific disease phenotypes, incorporation of patient-derived cells, genetic modifications, or integration with other brain region-specific organoids.
- Characterization - This could include morphological analyses, gene expression profiling, immunohistochemistry, and functional assays to verify the presence of cerebellar cell types and their appropriate organization within the organoid.
- Data Analysis and Report
- Follow-up
All cerebellar organoids developed in our labs are intended for use in vitro and are not to be used in clinical applications or for diagnostic purposes. We also offer flexibility in our services, including but not limited to:
| Services | Descriptions |
|---|---|
| Custom CNS Disease Modeling | We have optimized our neuroscience in vitro model platform with advanced technologies, high-quality facilities, and professional experts. 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. |
| Immunostaining | Immunostaining is a standard technique for the detection of specific proteins using antibodies. Immunostaining of organoid slices can further evaluate the spatial organization of specific cerebellar cell populations. |
| 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. |
Protocols for Cerebellar Organoid Generation
According to the protocol for dynamic 3D culture system, high-quality cerebellar organoids can be obtained for a series of biomedical applications.
Passaging and Maintenance of Human iPSCs in Monolayer Culture 
Seeding of Human iPSCs in the Bioreactor Differentiation and Maturation of Human iPSC-derived Aggregates in Cerebellar Organoids Preparation of Organoids for Cryosectioning and Immunohistochemistry Fig.2 Schematics show the protocol for cerebellar organoid generation.
Features of Cerebellar Organoid Culture System
- Repeatability to generate PSC-derived cerebellar-specific organoids
- Large-scale production
- Simple operation
Published Data
João Brás, et al. utilized control and Machado-Joseph disease (MJD) iPSCs to establish human brain organoids. They characterized these organoids in terms of brain development, cell type composition, and MJD-associated neuropathological markers to assess their value for modeling cerebellar disease.
Brain organoids presented markers of neural progenitor cell proliferation (Msi1, Notch1), neural differentiation (NeuroD1), neurotrophic factor (BDNF) production, and inhibitory (co-localization of VGAT and Gephyrin-positive spots) and excitatory (co-localization of VGlut and PSD95-positive spots) synapses. The data show increased neural progenitor cell proliferation and neuronal differentiation at day 25 and increased synaptic markers at day 40. In summary, other characterization data also suggest that the established organoids recapitulate important features of human brain development and exhibit cerebellar features, constituting a 3D cell-derived system to mimic cerebellar disease.
Fig. 3 Control and MJD brain organoids present markers of neural progenitors proliferation, neuronal differentiation, and synaptic function.2
Applications of Cerebellar Organoid
- High-throughput screening for drugs that restore cerebellar function
- Neurodevelopmental studies
- Evolutionary studies
- Gene function studies
- Disease modeling
- Drug testing
Creative Biolabs is one of the well-recognized experts who are professional in applying advanced platforms for a broad range of neurosciences research, now we provide the novel STEMOD™ neuroscience ex vivo models for our clients all over the world. We can enable you to free up your time for core work and projects. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.
FAQs
Q: What quality control checks do you have in place to ensure the quality and integrity of the cerebellar organoids?
A: Our quality control process includes multiple stages of confirmation and validation. First, we test the pluripotency of the starting stem cells. Then throughout organoid development, we perform periodic checks to confirm proper differentiation and maturation, as well as a final quality assessment of the finished organoids.
Q: How to handle and ship the cerebellar organoids safely?
A: We ship organoids in a specialized culture medium optimized for organoids’ health and stability. We also use temperature-controlled packaging for safe long-distance shipments. Additionally, we provide you with detailed instructions to ensure successful acclimation in your lab.
Q: How do I place an order and what information do you need from me?
A: To place an order, you can contact our customer service team or fill out the inquiry form on our website. We will need information about your specific research goals, the type of stem cells you wish to use, any desired customizations, and any other relevant experimental details. Once we have this information, we will provide a detailed project proposal and timeline.
Q: How long does it normally take for the creation of cerebellar organoids?
A: The timeline for generating cerebellar organoids can depend on several factors, such as the desired maturity and customizations required. Typically, from initial stem cell culture to mature organoid formation, the process usually spans 8-12 weeks. We provide regular updates throughout the development period.
Scientific Resources
References
- Silva, T.; et al. Scalable generation of mature cerebellar organoids from human pluripotent stem cells and characterization by immunostaining. JoVE (Journal of Visualized Experiments). 2020 (160): e61143.
- Brás, João, et al. "Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases." Scientific Reports 12.1 (2022): 12513.
For Research Use Only. Not For Clinical Use.