The Therapeutic Potential of the Stem Cell Secretome for Spinal Cord Repair: A Systematic Review and Meta-Analysis

Catriona Cunningham* (Corresponding Author), Marc Vives Enrich, Molly M Pickford, William Andrew Macintosh-Smith, Wenlong Huang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)
8 Downloads (Pure)


There is currently no effective treatment for spinal cord injury leaving around 90% of patients with permanent disabilities. Stem cell therapies are showing promise in preclinical studies of central nervous system injury and there is increasing evidence suggesting the improvements in functional recovery are mediated by paracrine actions. In this systematic review and meta-analysis, we aimed to determine the overall efficacy of stem cell secretome therapies in promoting recovery in preclinical models of spinal cord injury. We searched PubMed and Embase to identify relevant studies. A random effects meta-analysis was conducted using the restricted maximum likelihood estimator. We assessed risk of bias using a modified CAMARADES checklist. Publication bias was then assessed using funnel plots and trim-and-fill analysis. We identified 26 studies that met our inclusion criteria. Overall, stem cell secretome therapies conferred improvement in locomotor score (SMD: 2.30, 95% CI: 1.68-2.91), reduction in lesion size (SMD: 3.27, 95% CI: 2.06-4.48) and increased axonal
profiles in the lesion (SMD: 2.36, 95% CI: 1.02-3.71). We found there was significant asymmetry in the funnel plots for all three outcome measures, suggesting publication bias.
Trim-and-fill analysis estimated 19 and 3 unpublished studies in the locomotor score and axonal profiles datasets respectively. The median score on the modified CAMARADES checklist was 4 (IQR 4-5). Reporting of power calculations and allocation concealment was absent. The stem cell secretome is showing great potential as a therapy for spinal cord injury.
As the vast majority of studies began treatment acutely and favoured reduction in lesion size, we argue neuroprotection is likely the key mechanism of action. Future studies should focus on exploring the contribution of other mechanisms, the mediators involved and effect of treatment at a chronic stage of injury.
Original languageEnglish
Number of pages14
JournalOBM Neurobiology
Issue number4
Publication statusPublished - 14 Dec 2020

Bibliographical note

We would like to thank Drs Ya-Tzu Chen (Taipei Veterans General Hospital), May-Jywan Tsai (Taipei Veterans General Hospital), Kenji Kanekiyo (Aino University) and Yi Ren (Florida State University) for responding to our requests for clarification on their studies. We would also like to thank Dr Jack Rivers-Auty (University of Tasmania) for his advice on statistical analysis.
This work was supported by Graham and Pam Dixon and the Scottish Rugby Union.


  • Stem cells
  • cell therapy
  • spinal cord injury
  • neuroprotection
  • regeneration
  • systematic review
  • meta-analysis


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