ST2‑Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord

Stem Cell Reviews and Reports, 2023 · DOI: 10.1007/s12015-023-10618-x · Published: September 6, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the effect of conditioned medium from ST2 murine mesenchymal stem cells (ST2-CM) on dorsal horn (DH) neuron function using spinal cord organotypic cultures (SCOCs). The results show that ST2-CM increases neuronal activity and excitability in the DH, enhancing both intrinsic membrane properties and excitatory synaptic transmission. The study suggests that ST2-CM has a trophic role in maintaining network activity in spinal circuits, supporting its potential as a cell-free therapy for spinal cord injury and neuropathic pain.

Study Duration

3 days

Participants

Male and female CD1 mice

Evidence Level

Not specified

Key Findings

1
ST2-CM increases neuronal activity in the dorsal horn (DH) of spinal cord organotypic cultures (SCOCs), as measured by Fos expression.
2
ST2-CM enhances intrinsic DH neuron excitability, leading to increased spontaneous firing frequency and altered action potential kinetics.
3
ST2-CM potentiates calcium transients in DH neurons, shifting calcium transients from asynchronous single peak patterns to synchronous multipeaked waveforms.

Research Summary

This study demonstrates that ST2-CM enhances neuronal activity and synaptic wiring in the spinal dorsal horn. The findings support the trophic role of mesenchymal cells CM in maintaining network activity in spinal circuits. SCOCs represent a viable tool to probe mesenchymal cells' effect on intact neuronal networks.

Practical Implications

Therapeutic Potential

Mesenchymal stem cell-conditioned medium (MSC-CM) could represent a viable cell-free approach for treating neurological diseases affecting spinal neurons.

Drug Screening

Organotypic cultures of central neurons can be used for testing the efficacy of stem cell secretome, potentially shortening the distance between preclinical studies and therapeutic application.

Understanding Neuropathic Pain

Understanding the modulatory effects of MSC-CM on central circuits may provide insights into restoring altered circuits in pathological conditions, such as nerve or spinal cord injury.

Study Limitations

1
The study did not associate the observed effect with a specific cell population in the DH.
2
The study does not fully explain the functional impact on the sensory system.
3
Organotypic cultures are separated from peripheral and central connections, limiting direct in vivo translation.

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