ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
This article is part of the Research TopicMesenchymal Stem Cells and Derived Extracellular Vesicles as Next-Generation Biological Drugs for Tissue RegenerationView all 8 articles
Early Intervention with Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhances Survival and Functional Recovery after Spinal Cord Injury in Rats
Provisionally accepted
Barbara Porto Cipriano1,2Rachel Santana Cunha2
Thaís Alves de Santana2Kátia Nunes da Silva2Erick Correia Loiola1,2Júlio César Queiroz Figueiredo1,2
Elisama Araújo da Silva1,2Erik Aranha Rossi1,2
Adne Vitória Rocha de Lima1,2
Igor Campos Da Silva2Ravena Pereira do Nascimento3
Silvia Lima Costa3
Zaquer Suzana Munhoz Costa-Ferro1,2
Bruno Solano De Freitas Souza1,2*- 1Instituto Goncalo Moniz, Salvador, Brazil
- 2Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, Brazil
- 3Universidade Federal da Bahia, Salvador, Brazil
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Spinal cord injury (SCI) is a devastating condition with high mortality and limited treatment options. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as promising cell-free therapies due to their immunomodulatory and neuroprotective properties. Here, we evaluated the therapeutic potential of EVs derived from human umbilical cord MSCs in a rat model of SCI. Adult male Wistar rats were randomized into three groups: control, SCI, and SCI treated with a single intralesional dose of EVs. Locomotor recovery was assessed by the Basso, Beattie & Bresnahan (BBB) score, while survival, neuroinflammation, histological alterations, and biodistribution were systematically analyzed. EV administration improved 30-day survival, and locomotor performance from day 7, and was associated with sustained reductions in pro-inflammatory cytokines (IL-1β, TNF-α) alongside increased levels of anti-inflammatory cytokines (IL-10) and neurotrophic factors (BDNF). Histological and immunofluorescence analyses showed attenuated microglial activation and astrocytic reactivity, accompanied by reduced lesion size and glial scar formation. In vivo imaging demonstrated accumulation of labeled EVs at the injury site, with peak retention at day 7 post-injection. Together, these findings demonstrate that early intralesional delivery of MSC-EVs enhances survival, modulates the inflammatory response, and promotes functional recovery after SCI, supporting further translational development of EV-based interventions for SCI.
Keywords: spinal cord injury, Mesenchymal Stem Cells, extracellular vesicles, Survival, Neuroinflammation
Received: 30 Aug 2025; Accepted: 22 Oct 2025.
Copyright: © 2025 Cipriano, Cunha, de Santana, Silva, Loiola, Figueiredo, Silva, Rossi, Lima, Silva, Nascimento, Costa, Costa-Ferro and Souza. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bruno Solano De Freitas Souza, brunosolanosouza@gmail.com
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