Meta-analysis of stem cell transplantation for reflex hypersensitivity after spinal cord injury

Abstract

Stem cells have been used in novel therapeutic strategies for spinal cord injury (SCI), but the effect of stem cell transplantation on neuropathic pain after SCI is unclear. The current meta-analysis evaluates the effects of stem cell transplantation on neuropathic pain after SCI. We first conducted online searches of PubMed, Web of Science, China Academic Journals Full-text Database, and Wanfang Data for randomized controlled trials that compared stem cell transplantation and vehicle treatments in rodent models of neuropathic pain after SCI. Quality assessment was performed using Cochrane Reviewer’s Handbook 5.1.0, and meta-analysis was conducted with RevMan 5.3. Then, we developed a rat model of SCI and transplanted bone marrow mesenchymal stem cells to verify meta-analysis results. Twelve randomized, controlled trials (n = 354 total animals) were included in our meta-analysis and divided by subgroups, including species, timing of behavioral measurements, and transplantation time after SCI. Subgroup analysis of these 12 studies indicated that stem cell-treated animals had a higher mechanical reflex threshold than vehicle groups, with a significant difference in both rats and mice. The thermal withdrawal latency showed the same results in mouse subgroups, but not in rat subgroups. In addition, mesenchymal stem cell transplantation was an effective treatment for mechanical, but not thermal reflex hypersensitivity relief in rats. Transplantation showed a positive effect when carried out at 3 or 7 days post-SCI. Stem cell transplantation alleviates mechanical reflex hypersensitivity in rats and mice and thermal reflex hypersensitivity in mice after SCI.

Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials

“…Most basic researches and clinical trials also demonstrate that various cell types are generally feasible, but there still remains controversy exists due to significant heterogeneity, leaving us indeterminacy whether cell remedy possesses inherent merits in ameliorating patient's prognosis. After retrieving and reviewing the literature, especially in systematic review and meta-analysis, there are 11 articles including 3 clinical (1 BMSC, 1 OEC, 1 stem cell) [17,18] and 8 animal experiments (2 OEC, 1 BMSC, 3 stem cells, 1 SC, 1 NS/PC) [19][20][21][22][23][24][25][26][27]. However, most of the studies centering on a unitary cell type or self-control failure to provide us the comprehensive and detailed understanding of cell therapy, for example, whether different cell lines generate equivalent clinical outcome, what is the optimum time for cellular therapy, how many cells are suitable for the patient.…”

The Effect of GABAergic Cells Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review With Meta-Analysis

“…The SYRCLE's tool, based on the Cochrane Collaboration RoB Tool, aims to assess methodological quality and has been adapted to aspects of bias and plays a role in animal experiments ( 27 ). However, several previous meta-analyses of cell transplantation to alleviate neuropathic pain have not analyzed RoB based on the SYRCLE's tool ( 19 , 46 , 47 ). Another systematic review evaluated the therapeutic potential of regulatory T lymphocytes in periodontitis animal models and rated 42.11% of projects as unclear RoB ( 49 ).…”

“…The recovery of GABAergic neuron function therefore plays an important role in the treatment of pain. It was reported that stem cell transplantation could supplement the inhibitory interneurons in the CNS, restore the function of GABA neurons, and inhibit the mechanical hypersensitivity reaction (19). GABAergic neurons or neural progenitor cells (NPCs) may have similar potential to improve neuropathic pain in SCI or PNI models (20)(21)(22)(23)(24).…”

Use of Mesenchymal Stem Cells in Pre-Clinical Models of Spinal Cord Injury

“…For the mice, improvement in thermal withdrawal latency was observed. However, no improvement was seen in rat studies [72]. In a rat spinal cord hemisection model, BMSCs were noted to promote astrocyte migration to the injury epicenter.…”