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J Neurosurg Spine. 2019 Nov 1:1-16. doi: 10.3171/2019.8.SPINE19201. [Epub ahead of print]

A combination of mesenchymal stem cells and scaffolds promotes motor functional recovery in spinal cord injury: a systematic review and meta-analysis.

Author information

1Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2Department of Orthopedics and Neurosurgery, Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.
3Swedish Neuroscience Institute, Swedish Medical Center, Seattle, Washington.
4Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
5Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
6Department of Surgery and Spine Program, University of Toronto, Ontario, Canada.
7Department of Epidemiology and Biostatistics, School of Public Health, and.
8Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran; and.
9Brain and Spinal Injuries Research Center (BASIR), Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.



There is controversy about the role of scaffolds as an adjunctive therapy to mesenchymal stem cell (MSC) transplantation in spinal cord injury (SCI). Thus, the authors aimed to design a meta-analysis on preclinical evidence to evaluate the effectiveness of combination therapy of scaffold + MSC transplantation in comparison with scaffolds alone and MSCs alone in improving motor dysfunction in SCI.


Electronic databases including Medline, Embase, Scopus, and Web of Science were searched from inception until the end of August 2018. Two independent reviewers screened related experimental studies. Animal studies that evaluated the effectiveness of scaffolds and/or MSCs on motor function recovery following experimental SCI were included. The findings were reported as standardized mean difference (SMD) and 95% confidence interval (CI).


A total of 34 articles were included in the meta-analysis. Analyses show that combination therapy in comparison with the scaffold group alone (SMD 2.00, 95% CI 1.53-2.46, p < 0.0001), the MSCs alone (SMD 1.58, 95% CI 0.84-2.31, p < 0.0001), and the nontreated group (SMD 3.52, 95% CI 2.84-4.20, p < 0.0001) significantly improved motor function recovery. Co-administration of MSCs + scaffolds only in the acute phase of injury (during the first 3 days after injury) leads to a significant recovery compared to scaffold alone (SMD 2.18, p < 0.0001). In addition, the cotransplantation of scaffolds with bone marrow-derived MSCs (SMD 1.99, p < 0.0001) and umbilical cord-derived MSCs (SMD 1.50, p = 0.001) also improved motor function following SCI.


The findings showed that scaffolds + MSCs is more effective than scaffolds and MSCs alone in improving motor function following SCI in animal models, when used in the acute phase of injury.


ADSC = adipose tissue–derived stem cell; BBB = Basso, Beattie, Bresnahan locomotor rating scale; BMS = Basso mouse scale for locomotion; BMSC = bone marrow MSC; CI = confidence interval; EctoMSC = ecto-MSC; FEM = fixed-effect model; MSC = mesenchymal stem cell; PLGA = poly(lactic-co-glycolic acid); PMSC = placental MSC; SCI = spinal cord injury; SMD = standardized mean difference; UCMSC = umbilical cord MSC; recovery of function; spinal cord injury; stem cells; tissue scaffolds


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