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

Juárez, Esri H.; Wood, Chelsea R.; Davies, Rebecca; Kehoe, Oksana; Johnson, William E.B.; Merighi, Adalberto; Ferrini, Francesco

Abstract

Conditioned medium obtained from bone marrow-derived stem cells has been proposed as a novel cell-free therapy in spinal cord injury and neuropathic pain, yet the direct effect on spinal neuron function has never been investigated. Here, we adopted spinal cord organotypic cultures (SCOCs) as an experimental model to probe the effect of ST2 murine mesenchymal stem cells-conditioned medium (ST2-CM) on dorsal horn (DH) neuron functional properties. Three days of SCOC exposure to ST2-CM increased neuronal activity measured by Fos expression, as well as spontaneous or induced firing. We showed that the increase in neuronal excitability was associated with changes in both intrinsic membrane properties and an enhanced excitatory drive. The increased excitability at the single-cell level was substantiated at the network level by detecting synchronous bursts of calcium waves across DH neurons. Altogether, SCOCs represent a viable tool to probe mesenchymal cells' effect on intact neuronal networks. Our findings indicate that ST2-CM enhances neuronal activity and synaptic wiring in the spinal dorsal horn. Our data also support the trophic role of mesenchymal cells CM in maintaining network activity in spinal circuits. [Abstract copyright: © 2023. The Author(s).]

Citation

Juárez, E. H., Wood, C. R., Davies, R., Kehoe, O., Johnson, W. E., Merighi, A., & Ferrini, F. (2023). ST2-Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord. Stem Cell Reviews and Reports, 19, 2918-2928. https://doi.org/10.1007/s12015-023-10618-x

• Journal Article Type: Article
• Acceptance Date: Aug 28, 2023
• Online Publication Date: Sep 6, 2023
• Publication Date: Sep 6, 2023
• Deposit Date: Sep 13, 2023
• Publicly Available Date: Jan 16, 2024
• Journal: Stem Cell Reviews and Reports
• Print ISSN: 1550-8943
• Electronic ISSN: 2629-3277
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Pages: 2918-2928
• DOI: https://doi.org/10.1007/s12015-023-10618-x
• Keywords: Mesenchymal stem/stromal cells, Spinal cord organotypic cultures, Firing activity, Dorsal horn neurons, Calcium imaging
• Additional Information: Accepted: 28 August 2023; First Online: 6 September 2023; : ; : All animal experiments were approved by the Italian Ministry of Health (authorization 485/2017-PR).; : Not applicable.; : Not applicable.; : The authors declare that they have no conflict of interest.