Neural Stem Cells and Inflammation Modulation in Preclinical Spinal Cord Injury: A Systematic Review

Spinal cord injury (SCI) is a debilitating condition characterized by primary mechanical trauma followed by secondary neuroinflammation. Neural stem cells (NSCs) hold promise for SCI repair through their regenerative and immunomodulatory properties, including the promotion of anti-inflammatory macrophage phenotypes. However, the specific mechanisms by which NSCs modulate inflammation in preclinical models remain heterogeneous. This systematic review synthesizes evidence from rodent studies to elucidate these mechanisms and inform translational strategies. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025, using terms related to SCI, inflammation, and NSC transplantation. Preclinical studies involving NSC interventions in rodent SCI models were included if they assessed inflammatory outcomes. Data extraction focused on study characteristics, NSC administration, inflammation markers (e.g., cytokines, macrophage polarization), and functional recovery. Quality assessment followed SYRCLE guidelines, with narrative synthesis due to methodological heterogeneity. Ten studies met inclusion criteria, predominantly using rat or mouse contusion/compression models. NSC transplantation, often with adjuncts like hydrogels or genetic modifications (e.g., Wnt4, E-cadherin), consistently reduced proinflammatory markers (IL-1β, IL-6, and TNF-α) in 70% of studies (p < 0.05), with three demonstrating shifts toward anti-inflammatory M2 macrophages (e.g., increased CD206, arginase-1). Subacute timing enhanced efficacy, correlating with improved locomotor scores (e.g., BBB) and reduced glial scarring. However, 30% reported nonsignificant effects, attributed to chronic models or delivery methods. NSC transplantation modulates SCI inflammation by suppressing proinflammatory pathways and fostering M2 polarization, which facilitates repair. These findings point out the advantages of optimized NSC strategies for clinical translation.