Liao LQ, Liang RX, Ren ZX, Wang YY, Wei W, Li YS. Human umbilical cord blood-derived mesenchymal stem cell therapy in experimental spinal cord injury: A systematic review and meta-analysis. World J Stem Cells 2026; 18(10): 125423 [DOI: 10.4252/wjsc.125423]
Corresponding Author of This Article
Yong-Sheng Li, Manager, Laboratory Center, Guangdong Cord Blood Bank, No. 1 Nan Yun Fourth Road, Science City, Guangzhou 510663, Guangdong Province, China. life9999@yeah.net
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
research-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Li-Qiong Liao, Rui-Xia Liang, Department of Obstetrics, Guangdong Medical University Panyu He Xian Memorial Hospital, Guangzhou 511400, Guangdong Province, China
Zhu-Xiao Ren, Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou 511442, Guangdong Province, China
Ye-Yang Wang, Department of Spine, Orthopaedic Center, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China
Wei Wei, Yong-Sheng Li, Laboratory Center, Guangdong Cord Blood Bank, Guangzhou 510663, Guangdong Province, China
Author contributions: Liao LQ, Liang RX, and Li YS contributed to conceptualization, methodology, formal analysis, and drafting the original manuscript; Liao LQ and Liang RX contributed to data curation and investigation; Ren ZX, Wang YY, Wei W, and Li YS contributed to supervision; Ren ZX, Li YS, Wang YY, and Wei W contributed to review and editing; Ren ZX contributed to validation; Wang YY and Wei W contributed to resources and project administration. All authors read and approved the final manuscript.
AI contribution statement: During the preparation of this work, the authors used DeepSeek, Kimi, and Zhipu Qingyan (ChatGLM) to assist with R scripting for statistical analysis and English language polishing. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Yong-Sheng Li, Manager, Laboratory Center, Guangdong Cord Blood Bank, No. 1 Nan Yun Fourth Road, Science City, Guangzhou 510663, Guangdong Province, China. life9999@yeah.net
Received: July 7, 2026 Revised: August 4, 2026 Accepted: October 8, 2026 Published online: October 26, 2026 Processing time: 112 Days and 3.9 Hours
Abstract
BACKGROUND
Spinal cord injury (SCI) often causes persistent neurological deficits, and effective treatment options remain limited. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are promising therapeutic candidates. A rigorous synthesis of the preclinical evidence is needed to inform translational efforts.
AIM
To systematically evaluate the efficacy and safety of native, unmodified hUCB-MSC transplantation in SCI models, and explore dose-response relationships.
METHODS
We systematically searched PubMed, EMBASE, and Web of Science from inception through September 12, 2025, and updated the search on August 31, 2026. We included controlled animal studies. Data extraction and risk of bias assessment using the SYRCLE tool were conducted independently by two reviewers. Functional recovery was analyzed as standardized mean differences (SMDs) in random-effects models with the DerSimonian-Laird estimator and Hartung-Knapp-Sidik-Jonkman adjustment. The certainty of the evidence was evaluated using a modified GRADE framework.
RESULTS
Six studies involving 273 animals were included; 132 animals contributed to the functional-recovery meta-analysis. hUCB-MSC treatment was associated with significantly greater functional recovery [SMD = 2.35, 95% confidence interval (CI): 0.89-3.80, P = 0.009], with substantial heterogeneity (I2 = 81.8%). The certainty of the evidence was rated as low. Subacute administration (> 24 hours) was associated with significantly greater functional recovery (P = 0.033), whereas acute administration did not. No statistically significant increase in mortality risk was detected (relative risk = 1.20, 95%CI: 0.60-2.40). The low-dose subgroup (≤ 1 × 106 cells) showed a statistically significant effect (SMD = 1.40, 95%CI: 1.09-1.70, P < 0.001, I2 = 0%, k = 4), but this finding is hypothesis-generating and requires validation in larger studies.
CONCLUSION
Preclinical evidence suggests that native hUCB-MSC transplantation may improve functional recovery after SCI, although the overall certainty of the evidence is low. The apparent consistency of effects at low doses is a hypothesis-generating observation requiring further validation.
Core Tip: This systematic review and meta-analysis of six preclinical studies demonstrates that human umbilical cord blood-derived mesenchymal stem cell transplantation significantly improves functional recovery in experimental spinal cord injury, with a large effect size (standardized mean difference = 2.35). The certainty of evidence is low due to substantial heterogeneity and methodological limitations. A hypothesis-generating observation suggests that low doses (≤ 1 × 106 cells) may yield more consistent effects than higher doses, questioning the assumption of a simple linear dose-efficacy relationship. These findings provide an initial quantitative reference for future translational research.
