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Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization

Spinal Cord volume 62, pages 429–439 (2024)Cite this article

Subjects

Abstract

Study design

Animal studies

Objectives

To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI.

Setting

Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University.

Methods

Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen’s method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR.

Results

OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice.

Conclusions

OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

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Fig. 1: Identification and tracking of OM-MSCs delivered to the spinal cord injury site.
Fig. 2: OM-MSCs promote neural rehabilitation and functional behavioral recovery post SCI.
Fig. 3: Administration of OM-MSCs following SCI ameliorates inflammation and increases the M2 microglia proportion in vivo.
Fig. 4: Administration of OM-MSCs ameliorates inflammation and promotes the transformation of BV-2 cells from the M1 to M2 phenotype in vitro.
Fig. 5

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Data availability

Data supporting the findings of this study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (grant numbers 82172502 and 81974127).

Author information

Author notes

  1. These authors contributed equally: Hui Xie, Zheng-Zhao Liu.

Authors and Affiliations

  1. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Xin Wang, Ran Duan, Zhi-Lin Pang, Min-Na Zhang & Hui Xie

  2. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Xin Wang & Hui Xie

  3. Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Xin Wang, Chun-Gu Hong, Ran Duan, Zhi-Lin Pang, Min-Na Zhang & Hui Xie

  4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Hui Xie

  5. Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China

    Zheng-Zhao Liu

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Contributions

ZZL and XW conceived the study, designed the experimental procedures, analyzed the data, and prepared the manuscript. XW, CGH, RD, ZLP, and MNZ performed the experiments. HX provided the platform for the experiments, and ZZL and HX supervised the project.

Corresponding authors

Correspondence to Hui Xie or Zheng-Zhao Liu.

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The authors declare no competing interests.

Ethics approval

Animal experiments were approved by the Ethical Review Board of Xiangya Hospital of Central South University (No. 2017121175).

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Wang, X., Hong, CG., Duan, R. et al. Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization. Spinal Cord 62, 429–439 (2024). https://doi.org/10.1038/s41393-024-01004-6

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