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Creative Biolabs

Cortical Organoid Modeling Service

At Creative Biolabs, we specialize in generating human cortical organoids that faithfully replicate the complex cellular architecture and functional properties of the developing cerebral cortex. Our services empower neuroscientists to investigate cortical-specific neurodevelopmental processes, disease pathologies, and therapeutic interventions with unmatched biological precision.

Advantages of Cortical Organoids

  • Human-Specific Modeling: Human cortical organoids derived from human pluripotent stem cells replicate species-specific developmental processes, overcoming the limitations of animal models and enabling the study of human brain evolution and disorders.
  • Recapitulation of Cortical Architecture: These organoids mimic key molecular, cellular, and structural features of cortical development, including laminar organization, neural progenitor dynamics, and functional neural networks, providing valuable insights into both normal and pathological development.
  • Disease Modeling: They effectively model malformations of cortical development, such as microcephaly and Rett syndrome, by reproducing disease-specific phenotypes like altered proliferation, migration defects, and synaptic dysfunction, thereby aiding mechanistic studies and drug screening.
  • Functional Neural Activity: Human cortical organoids exhibit electrophysiological properties, including synchronized neural oscillations and synaptic activity, enabling the investigation of neurodevelopmental disorders linked to network dysfunction.
  • Modular Integration: They can be fused with other brain region-specific organoids, such as striatal and thalamic organoids, to study inter-regional interactions, including interneuron migration and corticothalamic connectivity, enhancing their utility in circuit-level research.

Our Services

  • Reproducible Human Cortical Organoids

Our protocol ensures highly consistent generation of human cortical organoids using standardized feeder-free, xeno-free differentiation methods. These organoids recapitulate key developmental stages, including neurogenesis, astrogenesis, and the formation of functional neural networks, with minimal batch-to-batch variability. Our human cortical organoids exhibit robust transcriptional and cellular reproducibility across multiple cell lines, making them ideal for disease modeling, drug screening, and developmental studies.

Fig.1 Immunofluorescent staining for brain regions and neuronal cell types in 35-day cortical organoids. (OA Literature) Fig.1 Visualizing brain regions and neuron types in 35-day cortical organoids via immunofluorescence.1,6

  • Robust Cortical Organoid Slices

We provide precision-cut organoid slices optimized for electrophysiological recording, live imaging, and high-content screening. These slices retain layered cortical architecture, synaptic activity, and network oscillations, enabling real-time analysis of neural dynamics. Their reliability makes them suitable for studying neurodevelopmental disorders, testing neuroactive compounds, and investigating circuit-level dysfunction.

Fig.2 Diverse cell populations segregate in hiPSC-derived ALI-Cos. (OA Literature) Fig.2 Human ALS/FTD cortical organoid slice cultures showed similar cortical morphogenesis and representation of major glial and neuronal cell types at 150 DIV.2,6

  • Vascularized Cortical Organoids

Our vascularized cortical organoids mostly integrate vascular endothelial cells with human cortical organoids to mimic neurovascular interactions and blood-brain barrier (BBB) development. This system enables studies on nutrient transport, hypoxia responses, and vascular-driven neurodegeneration. Enhanced vascularization improves organoid survival and maturation, supporting long-term experiments and translational applications.

Additionally, we can employ spheroid fusion strategies, including fusing preformed spheroids with cortical organoids, as well as co-differentiation strategies, such as using growth factors or gene editing to induce endothelial cell differentiation, based on your needs.

Fig.3 3 methods to generate vascularized cortical organoids. (OA Literature) Fig.3 Strategies for generating vascularized cortical organoids.3,6

  • Microglia-containing Cortical Organoids

By incorporating microglia into human cortical organoids, we model neuroimmune crosstalk, synaptic pruning, and inflammatory responses in neurodegenerative or infectious contexts. These chimeric organoids capture microglial activation, cytokine secretion, and phagocytic activity, offering insights into neuroinflammation mechanisms and therapeutic targeting.

  • Cortical Organoids-on-a-chip

Our cortical organoid-on-a-chip integrates a microfluidic platform with physiological hypoxia to replicate the fetal brain microenvironment. Advantages include enhanced neurogenesis, synaptogenesis, and neuronal maturation compared to conventional models, validated through advanced assays. Applications span drug screening (e.g., Tanshinone IIA neuroactivity), neurodevelopmental disorder studies, and disease modeling. Its biomimetic design enables high-throughput analysis of neural networks, offering a precise tool for exploring therapeutic interventions and brain development mechanisms.

Fig.4 Formation and validation of the human cortical organoid under hypoxic conditions. (OA Literature) Fig.4 Cortical organoid generation and validation under physiological hypoxia.4,6

  • Fusion Organoids with Cortical Organoids

To study inter-regional connectivity and circuit formation, we engineer fused assembloids combining human cortical organoids with ventral forebrain, thalamic, striatal, or spinal spheroids. These models replicate axon tract development, interneuron migration, and functional corticothalamic or cortico-striatal pathways, enabling the exploration of brain-wide network dysfunction in neuropsychiatric disorders.

Our Workflow

Fig.5 Cortical brain organoids modeling service workflow. (Creative Biolabs Original)

References

  1. Eigenhuis, Kristel N et al. “A simplified protocol for the generation of cortical brain organoids.” Front Cell Neurosci. 2023;17:1114420. doi:10.3389/fncel.2023.1114420
  2. Szebényi, Kornélia et al. “Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology.” Nat Neurosci. 2021;24(11):1542-1554. doi:10.1038/s41593-021-00923-4
  3. LaMontagne, Erin et al. “Recent advancements and future requirements in vascularization of cortical organoids.” Front Bioeng Biotechnol. 2022;10:1048731. doi:10.3389/fbioe.2022.1048731
  4. Zhi, Yue et al. “Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation.” Research (Wash D C). 2023;6:0273. doi:10.34133/research.0273
  5. Distributed under Open Access License CC BY 4.0 without modification.
  6. Distributed under Open Access License CC BY 4.0. The original image was modified.
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