# Human umbilical cord plasma derived exosome changed the miRNAs expression and inhibits inflammation response in traumatic spinal cord Injury

## TL;DR

Exosomes from human umbilical cord plasma reduce inflammation and improve recovery in spinal cord injury by modulating specific microRNAs.

## Contribution

The study identifies specific miRNAs modulated by exosome therapy in traumatic spinal cord injury and demonstrates their role in reducing inflammation and promoting recovery.

## Key findings

- Exosome treatment significantly improved motor and behavioral functions in SCI rats.
- Exosome therapy reduced inflammatory cytokine levels and cavity size in injured spinal cords.
- Exosomes modulated miR-19a-3p, miR-19b-3p, and miR-27b, which are linked to neuroinflammation and neural repair.

## Abstract

Spinal cord injury (SCI) is a debilitating neurological condition that leads to physical dependence, substantial financial burden, and psychological stress. Current for SCI, such as stem cell therapy, pharmacological interventions, and neural implants offer limited functional recovery. Among emerging strategies, exosome-based therapies in nerve damage can reduce neuroinflammation and promote neural repair by angiogenesis and neurogenesis. MicroRNAs (miRNAs) are key modulators of inflammatory and regenerative pathways in SCI. Specifically, miR-19a-3p, miR-19b-3p, and miR-27b have been implicated in regulating neuroinflammatory responses, neuronal survival, and tissue remodeling. Dysregulation of these miRNAs following SCI can exacerbate inflammation and hinder recovery. In this study, exosomes were extracted and characterized using flowcytometry for surface markers CD81 and CD9, scanning electron microscopy (SEM), dynamic light scattering (DLS), and Zeta potential analysis. Thirty-two female rats were randomly assigned into four groups: laminectomy only, contusion, contusion + PBS, and contusion + exosomes. SCI were induced using contusion model and thirty minutes after the injury, the exosome-treated group received an intravenous injection of 100 μl of exosomes via the tail vein for 7 days. Motor and behavioral functions were assessed through the open-field test, Basso, Beattie, and Bresnahan (BBB) scale and narrow beam test (NBT). Eight weeks after the SCI, real time PCR, Western blotting was utilized to assess changes in inflammatory cytokines, while histological changes were observed using hematoxylin and eosin (H&E) staining and stereology. In vivo experiments showed that the administration of exosomes significantly enhanced functional recovery and behavioral test outcomes following SCI. The treatment also resulted in a significant reduction in inflammatory cytokine levels and a marked decrease in the size of the cavity in the group treated with exosomes. Molecular analysis revealed that exosome therapy modulated the expression of miR-19a-3p, miR-19b-3p, and miR-27b, which are key regulators of neuroinflammation and neural repair. These findings suggest that exosomes hold strong therapeutic potential for treating SCI by modulating inflammation and promoting neural repair. Collectively, these findings indicate a potential mechanism through which exosomes exert their neuroprotective effects, particularly by regulating inflammatory and regenerative pathways.