AccScience Publishing / AN / Online First / DOI: 10.36922/AN025110022
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ORIGINAL RESEARCH ARTICLE

Local cytokine changes following fibrin-encapsulated mesenchymal stem cell-derived extracellular vesicle therapy in rat spinal cord injury

Ilyas M. Kabdesh1* ,  Ekaterina E. Garanina1 ,  Alexander A. Kostennikov1 ,  Albert A. Rizvanov1,2 ,  Yana O. Mukhamedshina1,2,3
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1 OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan (Volga region) Federal University, Kazan, Russia
2 Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, Kazan, Russia
3 Department of Histology, Cytology, and Embryology, Kazan State Medical University, Kazan, Russia
Advanced Neurology, 025110022 https://doi.org/10.36922/AN025110022
Received: 13 March 2025 | Revised: 9 July 2025 | Accepted: 8 August 2025 | Published online: 4 September 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Spinal cord injury (SCI) induces a prolonged and complex inflammatory response that contributes to secondary damage and influences functional recovery. Targeting this inflammatory milieu represents a promising therapeutic strategy. In this study, we investigated the effects of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) and encapsulated in a fibrin matrix (FM) on cytokine regulation in a rat model of SCI 60 days post-injury. MSCs were isolated from rat adipose tissue, and EVs were obtained using cytochalasin B-induced vesiculation. The EVs were encapsulated in FM and applied locally to the injury site at doses of 5 and 10 μg. The SCI rat models were divided into four groups: untreated, treated with FM alone, treated with 5 μg of EVs in FM (FM+EVs5), and treated with a 10 μg dose (FM+EVs10). A multiplex assay was employed to quantify the levels of 23 cytokines in spinal cord tissue homogenates. The application of FM alone altered cytokine levels, notably increasing granulocyte colony-stimulating factor (G-CSF) levels by 2.8-fold, which may be attributed to the hemostatic and bioactive properties of fibrin. Treatment with MSC-derived EVs resulted in a dose-dependent modulation of inflammatory responses. In the FM+EVs10 group, pro-inflammatory cytokines interleukin (IL)-1β and IL-5, as well as the anti-inflammatory cytokine IL-10, were significantly reduced compared to both the untreated and FM-alone groups, with IL-10 levels decreasing 2.4-fold. A similar trend was observed for IL-17A, which was 1.6-fold lower in the FM+EVs10 group compared to the FM-alone group. These findings suggest that fibrin-encapsulated MSC-derived EVs can modulate inflammation in chronic SCI and warrant further investigation as a therapeutic approach for neuroprotection and tissue repair.

Keywords
Spinal cord injury
Mesenchymal stem cells
Extracellular vesicles
Fibrin matrix
Cytokine modulation
Rats
Funding
This study was funded by the subsidy allocated to Kazan Federal University for state assignment (No. FZSM-2023- 0011) in the sphere of scientific activities.
Conflict of interest
The authors declare that they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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