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Stem cell therapy for locomotion recovery and neuropathic pain alleviation in spinal cord injury: an umbrella review and meta-analysis

Spinal Cord volume 63, pages 393–409 (2025)Cite this article

Subjects

Abstract

Study design

An Umbrella Review and Meta-analysis.

Objective

This umbrella review and meta-analysis aims to evaluate the efficacy of stem cell therapy for locomotion recovery and neuropathic pain alleviation in rodent models of spinal cord injury (SCI).

Methods

A comprehensive literature search was conducted in Medline, Embase, Scopus, and Web of Science until May 2024 to identify systematic reviews/meta-analyses on stem cell therapy for SCI. Original studies from these reviews were screened based on the predefined inclusion criteria. Data on locomotion, thermal hyperalgesia, and mechanical allodynia were extracted. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated and pooled to determine overall effect sizes. Subgroup analyses and meta-regressions were performed to investigate the optimal conditions for efficacy in each stem cell type.

Results

31 systematic reviews/meta-analyses with 323 original studies (516 experiments, 11,290 rodents) were included. Significant locomotion recovery was observed across stem cell types, with umbilical cord-derived mesenchymal stem cells (U-MSCs) (SMD = 2.34, 95% CI 1.76–2.93) and oligodendrocyte progenitor cells (OPCs) (SMD = 2.14, 95% CI 1.24–3.03) demonstrating superior efficacy. Only bone marrow-derived mesenchymal stem cells (BM-MSCs) alleviated mechanical allodynia (SMD = 1.33, 95% CI 0.61–2.05). Subgroup analysis showed that the efficacy of stem cell therapy is dependent on injury models, injury to treatment interval, stem cell dosage, and use of antibiotics/immunosuppressants. The certainty of evidence assessment showed high certainty for U-MSC in locomotion recovery, medium for BM-MSC in pain alleviation, and low for OPCs in locomotion recovery.

Conclusion

With moderate-to-high certainty, our study demonstrated superior efficacy of mesenchymal stem cells, particularly U-MSCs, when administered immediately post-injury at lower doses without antibiotics for locomotion recovery and BM-MSCs for pain alleviation. These findings suggest further clinical investigation of these stem cell types under optimal conditions.

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Fig. 1
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Fig. 2: Forest plot of the efficacy of different stem cells in locomotion recovery.
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Fig. 3: Forest plot of the efficacy of different stem cells in thermal hyperalgesia.
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Fig. 4: Forest plot of the efficacy of different stem cells in mechanical allodynia.
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Fig. 5
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Data availability

The dataset generated and analyzed during the current study is available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to acknowledge Dr. Kohansal, Dr. Fallahi, and Dr. Javaheri for their valuable assistance. However, their contributions do not meet the criteria for authorship.

Funding

This research has been supported by Tehran University of Medical Sciences and Health Services and Iran Ministry of Health and Medical Education (Grant number: 96-04-159-36946).

Author information

Authors and Affiliations

  1. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Amir Azimi, Amirmohammad Toloui, Mohammad Kiah, Hamed Zarei, Parsa Paridari, Sajjad Jabermoradi, Donya Pourkand & Mahmoud Yousefifard

  2. Rajaie Cardiovascular Medical and Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Amir Azimi & Mohammadhossein Mozafarybazargany

  3. Department of Emergency Medicine, NYC Health + Hospitals, Coney Island, New York, NY, USA

    Hamzah Adel Ramawad

  4. Department of Orthopedics and Neurosurgery, Rothman Institute, Thomas Jefferson University, Philadelphia, PA, USA

    Alexander R. Vaccaro

  5. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mostafa Hosseini

  6. Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Vafa Rahimi-Movaghar

Authors
  1. Amir Azimi
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  2. Amirmohammad Toloui
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  3. Mohammadhossein Mozafarybazargany
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  4. Mohammad Kiah
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  5. Hamed Zarei
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  6. Parsa Paridari
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  7. Sajjad Jabermoradi
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  8. Donya Pourkand
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  9. Hamzah Adel Ramawad
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  10. Alexander R. Vaccaro
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  11. Mostafa Hosseini
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  12. Mahmoud Yousefifard
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  13. Vafa Rahimi-Movaghar
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Contributions

Study design: MY, MH, VRM. Data gathering: DP, MM, HZ, MK, SJ, PP, AA. Data analysis: AA, AT, MM. Manuscript drafting: AA, MM, AT, HA. Critical revision: All authors.

Corresponding authors

Correspondence to Mahmoud Yousefifard or Vafa Rahimi-Movaghar.

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Competing interests

The authors declare no competing interests.

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During the preparation of this work, the authors used ChatGPT 3.5 in order to paraphrase the sentences and check the grammar of the text. After using the tool/service, the authors reviewed and edited the content as needed and took full responsibility for the publication’s content.

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Azimi, A., Toloui, A., Mozafarybazargany, M. et al. Stem cell therapy for locomotion recovery and neuropathic pain alleviation in spinal cord injury: an umbrella review and meta-analysis. Spinal Cord 63, 393–409 (2025). https://doi.org/10.1038/s41393-025-01104-x

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