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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Local cytokine changes following

fibrin-encapsulated mesenchymal stem
cell-derived extracellular vesicle therapy in rat

spinal cord injury

Ilyas M. Kabdesh * , Ekaterina E. Garanina 1 , Alexander A. Kostennikov 1 ,
1
Albert A. Rizvanov 1,2 , and Yana O. Mukhamedshina 1,2,3
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

Abstract

Spinal cord injury (SCI) induces a prolonged and complex inflammatory response
that contributes to secondary damage and influences functional recovery. Targeting
*Corresponding author:
Ilyas M. Kabdesh this inflammatory milieu represents a promising therapeutic strategy. In this study,
(ikabdesh@kpfu.ru) we investigated the effects of extracellular vesicles (EVs) derived from mesenchymal
Citation: Kabdesh IM, stem cells (MSCs) and encapsulated in a fibrin matrix (FM) on cytokine regulation in
Garanina EE, Kostennikov AA, a rat model of SCI 60 days post-injury. MSCs were isolated from rat adipose tissue,
Rizvanov AA, Mukhamedshina YO. and EVs were obtained using cytochalasin B-induced vesiculation. The EVs were
Local cytokine changes following
fibrin-encapsulated mesenchymal encapsulated in FM and applied locally to the injury site at doses of 5 and 10 µg.
stem cell-derived extracellular The SCI rat models were divided into four groups: untreated, treated with FM alone,
vesicle therapy in rat spinal cord
injury. Adv Neurol. 2025;4(4):77-87. treated with 5 µg of EVs in FM (FM+EVs5), and treated with a 10 µg dose (FM+EVs10).
doi: 10.36922/AN025110022 A multiplex assay was employed to quantify the levels of 23 cytokines in spinal cord
Received: March 13, 2025 tissue homogenates. The application of FM alone altered cytokine levels, notably
increasing granulocyte colony-stimulating factor (G-CSF) levels by 2.8-fold, which
Revised: July 9, 2025
may be attributed to the hemostatic and bioactive properties of fibrin. Treatment
Accepted: August 8, 2025 with MSC-derived EVs resulted in a dose-dependent modulation of inflammatory
Published online: September 4, responses. In the FM+EVs10 group, pro-inflammatory cytokines interleukin (IL)-1β
2025 and IL-5, as well as the anti-inflammatory cytokine IL-10, were significantly reduced
Copyright: © 2025 Author(s). compared to both the untreated and FM-alone groups, with IL-10 levels decreasing
This is an Open-Access article 2.4-fold. A similar trend was observed for IL-17A, which was 1.6-fold lower in the
distributed under the terms of the
Creative Commons Attribution FM+EVs10 group compared to the FM-alone group. These findings suggest that
License, permitting distribution, fibrin-encapsulated MSC-derived EVs can modulate inflammation in chronic SCI and
and reproduction in any medium, warrant further investigation as a therapeutic approach for neuroprotection and
provided the original work is
properly cited. tissue repair.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Spinal cord injury; Mesenchymal stem cells; Extracellular vesicles; Fibrin
regard to jurisdictional claims in
published maps and institutional matrix; Cytokine modulation; Rats
affiliations.

Volume 4 Issue 4 (2025) 77 doi: 10.36922/AN025110022