Stem cell transplantation and functional recovery after spinal cord injury: a systematic review and meta-analysis

Abstract

Spinal cord injury is a significant cause of motor dysfunctions. There is no definite cure for it, and most of the therapeutic modalities are only symptomatic treatment. In this systematic review and meta-analysis, the effectiveness of stem cell therapy in the treatment of the spinal cord injuries in animal models was studied and evaluated. A systematic search through medical databases by using appropriate keywords was conducted. The relevant reports were reviewed in order to find out cases in which inclusion and exclusion criteria had been fulfilled. Finally, 89 articles have been considered, from which 28 had sufficient data for performing statistical analyses. The findings showed a significant improvement in motor functions after cell therapy. The outcome was strongly related to the number of transplanted cells, site of injury, chronicity of the injury, type of the damage, and the induction of immune-suppression. According to our data, improvements in functional recovery after stem cell therapy in the treatment of spinal cord injury in animal models was noticeable, but its outcome is strongly related to the site of injury, number of transplanted cells, and type of transplanted cells.

Keywords: Contusions; Meta-analysis; Spinal cord injuries; Stem cell therapy.

Fig. 1. Flowchart of search that was carried out through five different electronic databases including MEDLINE, EMBASE, ProQuest, BIOSIS, and Scopus. Out of 2,270 articles that were found, 28 studies were subjected to a meta-analysis that is based on inclusion and exclusion criteria.

Fig. 2. Location of injuries. The site of injuries in the model of spinal cord injuries (SCIs) was primarily found to be localized at T10 level with the highest frequency.

Fig. 3. Animal model species for spinal cord injuries. The data collected from 3,241 animals. As it is evident, the most frequent animal that was used was rat and the lowest was rabbit.

Fig. 4. Route of cell injections. There were six different routes of cell injections to the spinal cord. Direct injection into the spinal cord was the most frequent method that was used. ISP, intra spinal; IV, intra venous; CSF, cerebro-spinal fluid; ISP. INT, intra spinal. intrathecal.

Fig. 5. Graft type. As it is obvious, allogeneic graft type of stem cells was the most common type that was performed and autograft was the least frequent graft type.

Fig. 6. Relative frequency of immuno-suppressant applications in spinal cord injuries. According to our data, using immuno-suppressant was not frequent in the cell transplantation after spinal cord injuries.

Fig. 7. Models of spinal cord injuries. In comparison with other available models, the most frequent traumatic spinal cord injury model was contusion model which was performed in 15 experiments.

Fig. 8. Types of stem cell using for transplantation. Mesenchymal stem cells were mostly used in comparison with other transplanted cell types. NPC, neuroprogenitor cell; MSCs, mesenchymal stem cell; NSC, neural stem cell; iPSC, induced pluripotent stem cells; OLC, oligodendrocyte cells.

Fig. 9. Forest plot of stem cell therapy on motor functions without considering the type of the stem cell [2456714151718192021222324252627282931323334353638]. The overall effect size of stem cell therapy on motor functions under both fixed (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.7–2.02) and random (OR, 4.36; 95% CI, 3.20–5.51) effect model was shown.

Fig. 10. Subgroup analysis of induced pluripotent stem cells (iPSC) effects on motor function [67183132]. The pooled effect size of induced pluripotent stem cell therapy on motor functions shows the effectiveness of iPSC therapy on motor functions under both fixed and random effect models. For each comparison, we calculated a standardized mean difference (SMD) with a confidence interval of 95% (95% CI), and then the pooled effect size was presented. Chi-square test was used for assessing of heterogeneity. A P-value of 0.1 or less considered as the existence of heterogeneity.

Fig. 11. Subgroup analysis of mesenchymal stem cell effects on motor function [245141719202223243536]. The pooled effect size of mesenchymal stem cell therapy on motor functions shows the effectiveness of mesenchymal stem cell therapy on motor functions under both fixed and random effect models. SMD, standardized mean difference; CI, confidence interval.

Fig. 12. Subgroup analysis of neural stem cells effects on motor function [3141525262728293436]. The pooled effect size of neural stem cell therapy on motor functions shows the effectiveness of neural stem cell therapy on motor functions under both fixed and random effect model. SMD, standardized mean difference; CI, confidence interval.