Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background/Aims: Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI. Methods: We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×10⁵), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection. Conclusion: Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions.

Progress in the Use of Induced Pluripotent Stem Cell-Derived Neural Cells for Traumatic Spinal Cord Injuries in Animal Populations: Meta-Analysis and Review

“…In addition, preimplantation scores were 0 to 1, indicating paralysis except for one study . Our conclusion is supported by the recent meta‐analysis from studies that used rats as experimental animal model reaching similar conclusions .…”

“…. Although, this manuscript was in preparation, a meta‐analysis reported effective outcomes in the use of iPSC‐derived neural cells for SCI treatments in rat models . Our meta‐analysis complemented this study, and our review included additional studies using mouse and nonhuman primates and included results from studies using NSCs from iPSCs, ESC, and wild‐type lines.…”

“…The following criteria are based on previous reviews . 1, Compliance with animal welfare regulations; 2, Publication in a peer‐reviewed journal; 3, description of animals used; 4, designation of strain; 5, number of animals per group; 6, description of level of injury; 7, randomly assigning animals to a specific group; 8, description of the control groups; 9, blindness of assessor; 10, description of statistical analysis; 11, statement of any potential conflict of interest.…”

“…[18]. Although, this manuscript was in preparation, a meta-analysis reported effective outcomes in the use of iPSC-derived neural cells for SCI treatments in rat models [19]. Our meta-analysis Figure 1.…”

“…Note: if all the above criteria were fulfilled, then those studies were included into the meta-analysis, with the exception of Tsuji: No immunosuppressant was administered nor was SCID mice used; however, iPSCs were cultured from own fibroblasts. Previous subgroup analyses indicate motor recovery outcome was significantly affected by the injury model (compression, contusion, and hemisection), intervention phase (subacute, acute, and chronic), and immunosuppression; thus, these criteria were included in order to screen out studies for the meta-analysis [19]. the null hypothesis μ iPSCs = μ control and the alternative hypothesis μ iPSCs > μ control , which assumes that the mean BMS score post-transplantation in the iPSCs group should be higher than the control group.…”