Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis

Abstract

ObjectiveTo compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).DesignA systematic review and Bayesian network meta-analysis.Data SourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials.Study SelectionWe included randomized controlled trials, case–control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.ResultsForty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0–0.91, low certainty) and FIM score at 12 months (42.83, 36.33–49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15–0.73, moderate certainty), the motor score at 6 months (4.43, 0.91–7.78, moderate certainty), light touch at 6 (10.01, 5.81–13.88, moderate certainty) and 12 months (11.48, 6.31–16.64, moderate certainty), pinprick score at 6 (14.54, 9.76–19.46, moderate certainty) and 12 months (12.48, 7.09–18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62–6.97, moderate certainty) and 12 months (5.54, 2.45–8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71–17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.ConclusionsPatients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.

Adverse events of cell therapy clinical trials in human chronic spinal cord injury, a systematic review and meta-analysis

“…The CSF leak, wound infection, and constipation were the more common severe AEs in our review. The CSF leakage has been more common severe AE in other studies [ 56 , 59 , 60 ]. The wound infection with Staph.…”

“…systematic review with meta-analysis, in 19 studies [ 60 ]. The other severe AE with less prevalence included autonomic dysreflexia, meningitis [ 59 ], and pseudo meningocele [ 59 , 60 ]. On the other hand, in the systematic review and meta-analysis by Tang, Q-R. et al., there was no reporting of wound infection, cerebrospinal fluid leakage, intracranial infection, or spinal cord diameter increasing.…”

The Efficacy of Different Material Scaffold-Guided Cell Transplantation in the Treatment of Spinal Cord Injury in Rats: A Systematic Review and Network Meta-analysis

“…In the natural materials cohort, mesenchymal stem cell is better at improving motor function in SCI rats, but there is no statistical significance. Recently, a systematic review of clinical cell transplantation shows that mesenchymal stem cell ranks first in most of the cells used for transplantation in improving the ASIA Impairment Scale (AIS) grade of SCI patients (Xu et al 2022 ). However, only in terms of improvement of motor function, neural stem cell is better than MSC, which is consistent with the results of our synthetic material cohort.…”

Neurotrophic and immunomodulatory effects of olfactory ensheathing cells as a strategy for neuroprotection and regeneration

“…Forty-four eligible trials, involving 1,266 SCI patients, investigated several cell-based treatments to improve functional independent misure (FIM) score. Among them, OEC transplantation proved to ameliorate the FIM score at 6 months, thus improving disease prognosis ( 114 ). However, a common consequence in these studies is the poor survival of transplanted cells, with survival rates ranging from 0.3 percent to 3 percent.…”