Cerebrovascular Disorder Organoid Modeling Service

Fig.1 Available methods of brain organoid vascularization.¹

Cerebrovascular disorders, such as ischemic and hemorrhagic stroke, are a leading cause of mortality and long-term disability worldwide. The development of effective neuroprotective and restorative therapies has been profoundly hindered by preclinical models that fail to capture the complex pathophysiology of the human brain. While animal models have species-specific differences in cerebrovascular architecture, traditional 2D cultures lack the three-dimensional interplay of the neurovascular unit (NVU). Even standard brain organoids, which recapitulate many aspects of neurodevelopment, are inherently limited by their lack of a functional vascular system.

Creative Biolabs overcomes this critical barrier with our advanced Cerebrovascular Disorder Modeling Service. We engineer vascularized brain organoids (vOrganoids) that reconstruct the human NVU in vitro. By integrating key vascular and glial cells, we create a physiologically relevant platform to investigate disease mechanisms, screen neuroprotective agents, and accelerate the development of next-generation stroke therapies.

Reconstructing the Human Neurovascular Unit (NVU) in a Dish

Our proprietary protocols move beyond simple neuronal cultures to build a functional, multi-component system that mimics the key features of human brain vasculature.

• Multi-lineage Cellular Composition: We begin with human iPSCs (patient-derived or CRISPR-engineered) and differentiate them into cortical neurons and glial cells. Crucially, we then co-culture these with iPSC-derived endothelial cells, pericytes, and astrocytes to form a complete NVU model.
• Self-Assembling Vascular Networks: Our optimized culture conditions promote the self-assembly of endothelial cells into complex, perfusable capillary-like networks within the 3D organoid structure. These networks are supported by pericytes and astrocytes, mimicking the natural cytoarchitecture of the brain.
• Functional Blood-Brain Barrier (BBB) Formation: The vascular networks within our organoids establish a functional barrier, characterized by the expression of tight junction proteins (e.g., ZO-1, Claudin-5) and physiological properties like selective permeability. This makes our vOrganoids an invaluable tool for studying BBB integrity and drug transport.

A High-Fidelity Platform for Cerebrovascular Disease Modeling

Our vascularized organoids enable the investigation of a wide range of cerebrovascular pathologies with unparalleled human relevance.

1. Ischemic Stroke Modeling: We simulate ischemic conditions in vitro using oxygen-glucose deprivation (OGD) protocols. This allows for the study of the ischemic cascade, including neuronal death, BBB breakdown, and neuroinflammatory responses, and provides a robust platform for screening neuroprotective compounds.
2. Hemorrhagic Stroke Modeling: By introducing blood components like heme, we can model the cellular toxicity and inflammatory damage associated with intracerebral hemorrhage, providing mechanistic insights and a testbed for novel therapeutics.
3. Modeling Genetic Vascular Disorders: We utilize patient-derived iPSCs to create models of inherited cerebrovascular diseases, including CADASIL, moyamoya disease, and cerebral cavernous malformations (CCM), allowing for the study of patient-specific disease mechanisms.
4. Drug Efficacy and BBB Permeability Studies: Our platform is ideal for assessing therapeutic candidates. Test not only the neuroprotective efficacy of your compound but also its ability to cross the blood-brain barrier to reach its target, a critical factor for CNS drug development.

Our Workflow

From Avascular Models to Functional Insights. Redefine Your Stroke Research.

Investigate cerebrovascular disease in a model that matters. Contact Creative Biolabs to learn how our vascularized brain organoids can advance your therapeutic pipeline.

Discuss Your Project with an NVU Expert

Reference

1. Song, Guini et al. "The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects." Frontiers in cellular neuroscience vol. 15 646921. 21 Jun. 2021, doi:10.3389/fncel.2021.646921. Distributed under Open Access License CC BY 4.0 without modification.