Whole Brain Organoid Modeling Service

At Creative Biolabs, we specialize in whole brain organoid models that recapitulate the complexity of human brain development and pathology. Unlike region-specific organoids, our whole brain organoid systems preserve inter-regional connectivity, cellular diversity, and functional neural network dynamics, offering researchers an unparalleled platform to study neurodevelopment, disease mechanisms, and therapeutic interventions in a human-relevant context.

Why Whole Brain Organoids?

• Human-specific modeling: Cerebral organoids recapitulate key features of human brain development, including outer radial glial cells (oRGs) and layered progenitor zone organization (ventricular and subventricular zones), absent in rodent models. This allows for the investigation of human-specific neurodevelopmental processes.
• Regional heterogeneity: These organoids self-organize into distinct, interconnected brain regions (e.g., dorsal/ventral forebrain, hippocampus, choroid plexus, retinal tissue), exhibiting spatial organization and inter-regional signaling that mimics in vivo complexity.
• Functional neurons: Organoids generate mature, functionally active neurons displaying calcium oscillations, glutamate responsiveness, and action potential-dependent signaling, facilitating electrophysiological analyses.
• Disease modeling: Successful modeling of microcephaly using patient-derived iPSCs has revealed premature neuronal differentiation and progenitor depletion, defects not observed in rodent models. This demonstrates the utility of organoids in studying neurodevelopmental disorders.
• Long-term culture: Structural complexity is maintained for up to 10 months, enabling extended developmental studies. Our 3D Matrigel/spinning bioreactor system optimizes nutrient exchange and tissue growth.
• Evolutionary insights: Comparative analyses with mouse organoids highlight human-specific developmental mechanisms, bridging the gap between animal models and human biology.

Our Services

• Cerebral Organoid Generation, Customization, and Characterization
  • Standardized protocols for reproducible whole brain organoid generation.
  • Custom organoid generation from customer-provided iPSCs.
  • Multiplexed immunofluorescence for post-fixation validation of cellular and regional identity (e.g., Pax6/TBR1, GFAP/S100β).
• Advanced Functional and Structural Analysis
  • Extracellular electrophysiology for measuring spontaneous neuronal activity, network dynamics, and synaptic function.
  • Calcium imaging for mapping neuronal activity and neurotransmitter responses in live organoids.
  • Electron microscopy (EM) for ultrastructural analysis of dendritic spines, synapses, and axon-dendrite connectivity.
• Disease Modeling and Drug Screening
  • Generation of disease models through iPSC reprogramming from patient somatic cells or genetic engineering of hiPSCs.
  • High-throughput neurotoxicity screening for profiling drug effects on organoid viability, synaptic density, and tau phosphorylation.
  • Rescue validation of gene therapies and small molecule therapeutics.
• Photostimulation and Optogenetics Integration
  • Generation of photosensitive organoids for light-responsive network modulation.
  • Integration of optogenetic tools for manipulating circuit activity.
• Customized Maturation and Co-Culture Systems
  • Optimized protocols for long-term maturation, including dendritic spine formation, myelination, and functional network development."
  • Co-culture with endothelial cells for vascularization and modeling of the blood-brain barrier.

Case Studies

Case Study 1: ZIKV Infection and Alzheimer's Disease: Whole Brain Organoid Modeling

This study demonstrated the use of human iPSC-derived whole brain organoids to model Zika virus (ZIKV)-induced Alzheimer's disease pathology. ZIKV infection induced endoplasmic reticulum (ER) stress, activating the PERK-eIF2α pathway, which led to increased BACE1 and GSK3α/β expression, resulting in Aβ plaque and p-Tau accumulation, respectively. AD organoids exhibited exacerbated Aβ/p-Tau accumulation, which was reversed by PERK inhibitors, highlighting ER stress as a potential driver of AD progression.

Fig.1 Potential impact of ZIKV infection on Aβ accumulation via increased BACE levels.1,3

Fig.2 Possible ZIKV-mediated increase in p-TAU levels in AD organoids through GSK3α/β.1,3

Case Study 2: Modeling Machado-Joseph Disease With Whole Brain Organoids

Researchers developed whole brain organoids from control and Machado-Joseph disease (MJD) patient-derived iPSCs to model cerebellar neurodegeneration. Organoids recapitulated key developmental features, including ventricular-like zones, neuronal-glial interactions, and cerebellar markers. MJD organoids showed delayed maturation and increased ataxin-3 aggregates, mirroring disease pathology. This platform allows for mechanistic studies of cerebellar dysfunction and therapeutic testing.

Fig.3 Replication of core brain architecture in control and MJD whole brain organoids, demonstrating ventricular-like zones, neural progenitors, developing neurons, and glial networks.2,3

Our Workflow

To discuss your Whole brain organoid projects, please contact Creative Biolabs!

References

1. Lee, Seung-Eun et al. “Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.” Cell Death Discov. 2022;8(1):153.
2. Brás, João et al. “Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases.” Scientific reports vol. 12,1 12513. 22 Jul. 2022, doi:10.1038/s41598-022-16369-y
3. Distributed under Open Access License CC BY 4.0 without modification.