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A High-Resolution Multimodal Platform for Decoding Enteric Neuroimmune Interactions in Inflammatory Bowel Disease

September 5, 2025

Cell Symposia: Neuro-immune axis - Charting the periphery

Elisabet Rosas Canyelles, Ph.D.

Keywords: R3200 Platform, CellCage™ technology, Enteric nervous system, IBD (Inflammatory Bowel Disease), Neuroimmunology, Single-cell transcriptomics, Longitudinal analysis

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This research introduces a high-resolution multimodal workflow designed to decode complex enteric neuroimmune interactions in Inflammatory Bowel Disease (IBD). Utilizing the R3200 Platform and CellCage™ technology, the study captures longitudinal functional data and transcriptomic profiles from individual enteric neurons and immune cells. By preserving the spatial and functional context of these delicate cell types, the platform provides new insights into the cellular crosstalk driving intestinal inflammation and disease progression.

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Case Study: Functional Profiling of Microglia in Neuroinflammation

Link microglial behavior to gene expression at single-cell resolution, for insight into neuroinflammation, drug response, and immune dysfunction in CNS disease.

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Phagocytosis assay in CellCage enclosures - (click to expand image).

Researchers used the Cellanome R3200 to enclose individual microglia with fluorescent particles and track phagocytosis over 12 hours via fluorescent imaging. Each cell’s transcriptome was then sequenced, linking activity levels to gene expression.

What they found:

High-activity microglia upregulated genes in complement signaling, lipid metabolism, and lysosomal function–key pathways in neuroinflammation and repair.

Why it matters:

This approach overcomes key limitations in standard assays by capturing phagocytic function and gene expression in the same individual cells without dissociation, pooling, or inference. It enables a direct, scalable readout of immune heterogeneity, and reveals the transcriptional programs driving effective or impaired microglial responses.

‍What’s next:

Extend to co-cultures by layering enclosed microglia over intact neuronal networks. Study how cell-cell interactions shape phagocytic behavior and fate. Combine with cytokines, CRISPR libraries, or immunotherapies to generate time-resolved, multi-modal datasets that can be used for MoA analysis, early biomarker discovery, and AI-guided modeling in CNS disease.

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Case Study: Modeling Synapse Formation and Developmental Trajectories in 3D

Track development, function, and gene expression in intact neurospheres, a human-relevant 3D model increasingly vital as regulators move away from animal studies.

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Neurospheres in windowed cages that allow them to reach out to form a synapse - (click to expand image).

Stem-cell-derived neurospheres offer a robust 3D model of early brain development, but standard assays disrupt their structure and miss critical dynamics.

Approach:

Using the Cellanome R3200, the research team explored,

Hundreds of intact neurospheres (100–200 cells each) were cultured inside individual CellCage™ enclosures.
Axon extension, synapse formation and calcium activity were tracked over multiple days.
End-point RNA-Seq was linked back to each neurosphere’s functional behavior.
UMAP clustering revealed lineage-specific gene programs, validated by fluorescent markers.

‍What's next:

This lays the groundwork for CRISPR-based multimodal screens to probe mechanisms of development, degeneration, and repair within preserved 3D architecture.

‍Why it matters:

As the FDA and others move to reduce reliance on animal models, human-relevant in vitro systems like this are increasingly essential.

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FAQ's

How does the R3200 Platform facilitate the study of enteric neuroimmune interactions?

The R3200 Platform enables the simultaneous, longitudinal monitoring of enteric neurons and immune cells within the same microenvironment. By capturing real-time interactions and physiological changes, the platform allows researchers to map the functional signaling pathways that occur between the nervous and immune systems in the gut.

What role does CellCage™ technology play in decoding IBD mechanisms?

CellCage™ technology provides a stable, non-destructive environment for sensitive enteric cell types. This allows for the precise tracking of cell-cell interactions over time without the stress of traditional dissociation, ensuring that the resulting transcriptomic data reflects the true physiological state of the cells during an inflammatory response.

Why is a multimodal approach necessary for studying the neuro-immune axis in IBD?

IBD is characterized by complex interactions that cannot be fully understood through gene expression alone. A multimodal approach on the R3200 Platform combines visual phenotyping—such as neuronal firing or cytokine release—with transcriptomics, providing a comprehensive view of how neuroimmune crosstalk contributes to intestinal dysfunction.

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