AUTHOR=Cipriano Barbara Porto , Cunha Rachel Santana , Santana Thaís Alves de , Silva Kátia Nunes da , Loiola Erick Correia , Figueiredo Júlio César Queiroz , Silva Elisama Araújo da , Lima Adne Vitória Rocha de , Rossi Erik Aranha , Silva Igor Campos da , Nascimento Ravena Pereira do , Costa Silvia Lima , Costa-Ferro Zaquer Suzana Munhoz , Souza Bruno Solano de Freitas 

TITLE=Early intervention with extracellular vesicles derived from human umbilical cord mesenchymal stem cells enhances survival and functional recovery after spinal cord injury in rats

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1695914

DOI=10.3389/fphar.2025.1695914

ISSN=1663-9812

ABSTRACT=IntroductionSpinal 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.MethodsAdult 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.ResultsEV 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.DiscussionTogether, 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.