Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway.
Overview
- State Key Laboratory of Traditional Chinese Medicine Syndrome, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Department of Orthopedic Surgery The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Spinal Minimally Invasive Department, Spinal Degenerative Disease Prevention and Treatment Research Team The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Laboratory of Osteology and Traumatology of Traditional Chinese Medicine, Lingnan Medical Research Center Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Department of Orthopedics The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Dalian Ocean University Dalian Liaoning China
- College of Physical Education and Health Guangzhou University of Chinese Medicine Guangzhou Guangdong China
- Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine Zhongshan Guangdong China
- Department of Orthopedics Dongguan Hospital of Guangzhou University of Chinese Medicine Dongguan Guangdong China
- Department of Orthopedics (Articular Surgery) The Zhuhai Hospital of Guangdong Province Hospital of Chinese Medicine Zhuhai Guangdong China
Abstract
Objective: Spinal cord injury is a devastating neurological disorder. The transplantation of mesenchymal stem cell‐derived exosomes has shown great promise. Wnt5a has been reported to promote neuronal differentiation and spinal cord regeneration. However, its mechanistic role when delivered via exosomes remains unclear. In the present study, the function and underlying mechanism of Wnt5a in promoting neuronal differentiation and spinal cord repair were investigated using bone marrow mesenchymal stem cell‐derived exosomes.
Methods: This study initially constructed Wnt5a‐overexpressing BMSCs and isolated and characterized their exosomes. Subsequently, in vitro experiments were conducted to detect markers of neurons, astrocytes, and microglia. This was followed by high‐throughput sequencing to analyze related pathways. Finally, in vivo experiments were performed, in which rats were divided into the Sham group, the SCI group, the Exo group, and the pLV‐Exo‐Wnt5a group. The effects of exosomes in vivo were analyzed through histological, behavioral, electrophysiological, western blot, PCR, and immunofluorescence assays.
Results: Our results demonstrated that Wnt5a‐enriched BMSC‐Exos significantly enhanced the proliferation and neuronal differentiation of neural stem cells, while suppressing astrocyte formation. High‐throughput RNA sequencing revealed an association between Wnt5a and the NF‐κB signaling pathway. Intervention with lipopolysaccharide confirmed that Wnt5a exerts a suppressive effect on this pathway. In vivo, the transplantation of Wnt5a‐modified BMSC‐Exos facilitated the polarization of microglia towards an anti‐inflammatory M2 phenotype, promoted neurogenesis, reduced astrocyte accumulation, improved spinal cord tissue architecture, and led to better motor function recovery.
Conclusion: Collectively, these findings indicate that Wnt5a enhances the neuroregenerative potential of BMSC‐Exos by modulating immune responses and suppressing neuroinflammation, likely through inhibiting the NF‐κB signaling pathway.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Data links
- ncbi.nlm.nih.gov/
geo — NCBI; found in “Data Availability Statement”
Data Availability Statement
The data used to support the findings of this study are available from the corresponding authors upon request. RNA‐Seq data are deposited in the NCBl Gene Expression Omnibus (GEO) repository at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 7 keywords, 13 MeSH terms, 4 funders, 64 references.
Cite
This paper
Luo, D., Feng, E., Chen, L., Ni, K., Luo, S., Ma, L., Wu, Y., Hu, Z., Lin, D., Zhang, B., Yin, C., Guo, D., Liang, C., & Li, X. (2026). Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway. CNS neuroscience & therapeutics, 32(4), e70834. https://
BibTeX
@article{luo2026wnt5a,
author = {Luo, Dan and Feng, Enhui and Chen, Ling and Ni, Ke and Luo, Sheng and Ma, Lin and Wu, Yuting and Hu, Zhifeng and Lin, Dingkun and Zhang, Binshan and Yin, Chaoyi and Guo, Da and Liang, Chaolun and Li, Xing},
title = {{Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway}},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = apr,
volume = {32},
number = {4},
pages = {e70834},
publisher = {Wiley},
issn = {1755-5930},
doi = {10.1002/
url = {https://
pmid = {41885803},
pmcid = {PMC13140915}
}
RIS
TY - JOUR
AU - Luo, Dan
AU - Feng, Enhui
AU - Chen, Ling
AU - Ni, Ke
AU - Luo, Sheng
AU - Ma, Lin
AU - Wu, Yuting
AU - Hu, Zhifeng
AU - Lin, Dingkun
AU - Zhang, Binshan
AU - Yin, Chaoyi
AU - Guo, Da
AU - Liang, Chaolun
AU - Li, Xing
TI - Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway
T2 - CNS neuroscience & therapeutics
J2 - CNS Neurosci Ther
PY - 2026
DA - 2026/
VL - 32
IS - 4
SP - e70834
SN - 1755-5930
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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