PNS-3D Technology

Investigate Therapeutic Risk to the Peripheral Nervous System with Human Nerve Organoids

Peripheral neuropathy affects millions worldwide, characterized by debilitating sensory, motor, and autonomic impairments. Address these challenges with PNS-3D technology—a human, complex in vitro organoid model designed for preclinical testing of disease-, medication-, and toxin-induced neuropathies.

PNS-3D Organoids

PNS-3D Organoids support clinically relevant electrophysiology and nerve conduction studies by generating 10 mm in vitro nerves within 49 days. Cultured in custom 24-well plates with embedded electrodes, they provide functional and morphological insights into peripheral neuropathies, neurodegenerative diseases, and chemotherapy-induced nerve damage.

Cell Types

PNS-3D Organoids are composed of human iPSC-derived sensory neurons and primary Schwann cells co-cultured in a 3D matrix. Sensory neurons provide functional signaling capabilities, while Schwann cells support axonal growth and myelination. Together, these cell types self-organize into structured nerve-like tissues that replicate key cellular interactions of the peripheral nervous system.

Assays

Electrically Evoked Electrophysiology

Electrically Evoked Electrophysiology (EEA) captures clinically relevant human nerve function data by measuring conduction velocity, stimulus threshold, and response amplitude. These key endpoints are integrated into the Velocity Density Index (VDI).

Morphological Neurite Degeneration Analysis

A quantitative assessment of structural changes in nerve fibers captures subtle functional and morphological alterations induced by diseases or therapeutic agents.

Downstream Analysis

Samples are available for advanced mechanistic analyses, including RNA sequencing, western blotting, and mass spectrometry, facilitating deeper understanding of molecular responses and therapeutic effects.

Use Case 01

ADC Neurotoxicity

PNS-3D technology can quantify ADC neurotoxicity and stability through electrophysiology outputs and serves as an effective tool that provides extensive functional insights into known and novel ADCs for drug development purposes.

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IC50 curves for trastuzumab-MMAE, trastuzumab-DM1, and free MMAE overlay functional electrophysiology (black) with nerve morphology (blue); in every case, neuronal activity declines at far lower concentrations than structural integrity, highlighting the PNS-3D Organoids' ability to flag neurotoxic effects well before overt morphological damage appears.

Use Case 02

Chemotherapy-Induced Peripheral Neuropathy

With up to 70% of cancer patients experiencing chemotherapy induced peripheral neuropathy (CIPN), PNS-3D has repeatably shown accurate response data consistent with accepted research values through years of rigorous testing for common chemotherapeutic agents causing CIPN.

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Overview contrasting healthy PNS-3D organoids (left column) with chemotherapeutic-induced peripheral neuropathy (right column): intact sensory neurons and supportive Schwann cells give rise to robust electrophysiological activity and continuous nerve fibers, whereas CIPN produces neuron and/or Schwann-cell loss, silenced electrophysiology, and fragmented axons.

Use Case 03

SARM1 Inhibition & Neuroprotection

PNS-3D investigated neuroprotective properties of newly developed compounds designed to inhibit Sterile alpha and TIR motif containing 1 (SARM1) in human samples, designed to prevent or delay CIPN. Comparisons of functional and morphological metrics from SARM1 inhibitors provide customers with neuroprotection efficacy estimates.

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Population-level nerve conduction contrasting vehicle (column 1) with three SARM1 inhibitors with vincristine (columns 2–4) across successive time points (rows): NB-7 and WX-02-37 sustain electrophysiological responses close to baseline long after dosing, whereas DSRM-3716 fails to avert the rapid functional collapse seen with vincristine alone.

Investigate Therapeutic Risk to the Peripheral Nervous System with Human Nerve Organoids

A Complex in vitro Model

ADC Neurotoxicity

Chemotherapy-Induced Peripheral Neuropathy

SARM1 Inhibition & Neuroprotection

PNS-3D Technology Resources