Umbilical cord-derived exosomes alleviate spinal cord injury by regulating microglial polarization through miR-340-5p-mediated modulation of the JAK/STAT3 signaling pathway

Sep 1, 2025Scientific reports

Umbilical cord exosomes may help spinal cord injury by changing immune cell behavior through miR-340-5p's control of the JAK/STAT3 pathway

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Abstract

derived from human umbilical cord mesenchymal stem cells may significantly reduce inflammation and SCI progression in a mouse model.

Exosomes hinder M1 polarization in BV2 cells, which is associated with reducing inflammation.
There is a decrease in inflammatory markers such as IL-6, TNF-α, and IL-1β following treatment with hucMSC-derived exosomes.
The expression of beneficial proteins like Arg1 and CD206 is enhanced, which may indicate a shift towards anti-inflammatory responses.
The mechanism involves increased levels of miR-340-5p, which appears to suppress the JAK/STAT3 signaling pathway.
This approach suggests a potential new therapy for spinal cord injury, though further studies are needed to confirm these findings.

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Spinal cord injury (SCI) is a condition of the central nervous system, results in impairments in both sensory and motor functions. Presently, there exists a deficiency in efficacious therapies. Nonetheless, employing , a derivative of human umbilical cord mesenchymal stem cells (hucMSCs), is proven to be a successful approach in treating SCI, yet the exact way they function is still not well understood. Our research involved conducting a laminectomy on mice's thoracic T8-T10 and subsequently striking the revealed spinal cord using an altered Allen's weight descending apparatus (8 g, height 50 mm, 8 g × 50 mm) to create a model for SCI animals. To create a model of BV2 inflammation, BV2 cells underwent a 24-hour treatment with 1 µg/mL LPS. The expression of related genes and proteins was identified using RT‒qPCR and western blot. ELISA, immunofluorescence staining, and HE staining were employed to assess the polarization of BV2 cells and spinal cord tissue damage in mice. The research indicated that exosomes originating from hucMSCs are capable of markedly hindering the M1 polarization in BV2 cells, diminishing inflammation, and lessening the progression of SCI in vivo. From a mechanistic standpoint, exosomes originating from hucMSCs suppressed iNOS and CD16 levels, enhanced Arg1 and CD206 expression, lessened BV2 cells' M1 polarization, and concurrently suppressed LPS-triggered inflammatory cytokines IL-6, TNF-α, and IL-1β, ultimately easing LPS-triggered inflammation and mitigating SCI progression. The impact of exosomes derived from hucMSCs primarily resulted from the enhancement of miR-340-5p expression, which in turn suppressed the JAK/STAT3 signaling pathway. The findings of our research indicate that exosomes derived from hucMSCs could represent an innovative approach in treating SCI.

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Increase in expression

Observed in BV2 cells after treatment with -Exos.

not provided

Higher Basso Mouse Scale scores

Compared to untreated SCI mice.

not provided

Decrease in pro-inflammatory cytokines

Observed in spinal cord tissues after -Exos treatment.

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Umbilical cord-derived exosomes alleviate spinal cord injury by regulating microglial polarization through miR-340-5p-mediated modulation of the JAK/STAT3 signaling pathway

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