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Treatment with mesenchymal stem cells in a porcine model of sepsis: Assessment of the central nervous system

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Author(s):
Zboril, Sabrina ; Schmidt, Andre P. ; Maia, Debora R. Ramos ; Sanches, Talita R. ; Neto, Amaro N. D. ; Andrade, Lucia ; Oses, Jean P. ; Moreira, Fernanda P. ; Auler Jr, Jose Otavio C. ; Otsuki, Denise A.
Total Authors: 10
Document type: Journal article
Source: Neuroscience Letters; v. 862, p. 9-pg., 2025-07-27.
Abstract

Sepsis remains a leading cause of intensive care unit admissions and a significant public health challenge worldwide. Despite efforts, the development of specific therapies for sepsis has been limited. Mesenchymal stem cell therapy, particularly with cells derived from the human umbilical cord (hUC-MSC), has shown promise in animal studies. This study evaluated the use of hUC-MSC in a porcine model of sepsis induced by fecal peritonitis, focusing on hemodynamic and metabolic effects, inflammatory response, and central nervous system impact. Twenty-two pigs were randomized into a control group receiving fluids, vasopressors, and antibiotics, and a treatment group receiving the same interventions plus hUC-MSC infusion. Hemodynamic parameters, acid-base status, cytokine levels in serum and cerebrospinal fluid (CSF), and neuron-specific enolase were assessed over 24 h. Histopathological analysis of the hippocampus was performed post-mortem. No significant differences were observed between groups regarding hemodynamic and metabolic parameters or serum cytokine levels. While interleukin-1 beta levels in CSF increased in all animals' post-sepsis induction, interleukin-10 levels were significantly higher in hUC-MSC-treated animals. Histopathological analysis revealed reduced congestion, vasodilation, and neuronal karyolysis in the hippocampus of the treatment group. These findings suggest that while hUC-MSC therapy does not significantly impact hemodynamics, metabolism, systemic inflammation, or mortality in septic shock, it may offer neuroprotective effects. Further studies are required to elucidate the mechanisms underlying these potential neuroprotective properties of hUC-MSC in sepsis. (AU)