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Updated: May 22, 2026
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Three-Dimensional Motor Nerve Organoid Generation
Published on: September 24, 2020
Development of a human iPSC-derived corticospinal tract-on-a-chip
Andriana Charalampopoulou1, Arens Taga1, Khalil Rust1
1Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA.
Cell Reports Methods
|May 20, 2026
Summary
Researchers developed a human stem cell model to study corticospinal neuron (CSN) and spinal motor neuron (SpMN) connections. This platform aids neurodegenerative disease research and therapy development for corticospinal tract disorders.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Biotechnology
Background:
- Corticospinal tract degeneration causes disability in neurodegenerative diseases.
- Modeling human corticospinal neuron (CSN) pathology and connectivity is difficult due to interspecies differences.
Purpose of the Study:
- To develop a human induced pluripotent stem cell (hiPSC)-based microfluidic platform for modeling human CSN and spinal motor neuron (SpMN) connectivity.
- To enable the study of neural cell interactions by incorporating regionally specific astrocyte subtypes.
Main Methods:
- Utilized a hiPSC-based microfluidic platform with CSNs, SpMNs, and specific astrocyte subtypes.
- Employed multielectrode array electrophysiology for temporal network maturation analysis.
- Applied retrograde labeling and optogenetic strategies to demonstrate and validate synaptic connectivity and functional relevance.
Main Results:
- Demonstrated temporal maturation of the CSN-SpMN network in the microfluidic platform.
- Confirmed synaptic connectivity between human CSNs and SpMNs using retrograde labeling.
- Validated the functional relevance of the model through optogenetic activation and glutamate receptor antagonism.
Conclusions:
- The developed hiPSC-based microfluidic platform effectively models human corticospinal connectivity.
- This versatile model allows for the study of neurodegenerative diseases affecting the corticospinal tract.
- The platform supports future development of targeted therapies for CSN disorders.
