hUC-MSCs transplantation promotes neurological recovery by ameliorating spinal cord injury and hippocampal synaptic remodeling in female mice

Introduction: Spinal cord injury (SCI) induces not only local spinal cord pathology but also distal brain dysfunction, causing multi-dimensional impairments in motor, emotional, and cognitive functions. Human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation has emerged as a promising therapeutic strategy for SCI, but whether it concurrently improves pathological alterations in both the spinal cord and brain remains unclear. Methods: After establishing a mouse model of spinal cord contusion, hUC-MSCs were transplanted intrathecally starting 7 d post-injury and administered weekly for 4 wk. This study evaluated the effectiveness of hUC-MSCs transplantation in promoting neurological functional recovery in female mice with SCI through multi-dimensional behavioral tests. In addition, histopathological staining, immunofluorescence staining, and western blotting were performed to evaluate pathological changes in the spinal cord and hippocampus after hUC-MSCs transplantation. Results: hUC-MSCs transplantation significantly improved hindlimb locomotor function and alleviated anxiety-like and depression-like behaviors, as well as long-term memory deficits in female mice with SCI. At the spinal cord level, hUC-MSCs increased IL-10 expression, reduced glial activation, and promoted axonal regeneration. In the hippocampus, hUC-MSCs alleviated neuroinflammation and region-specific abnormalities in synaptic remodeling and microglial synaptic pruning. Conclusion: This study demonstrated that hUC-MSCs transplantation concurrently improved pathological alterations in both the spinal cord and hippocampus after SCI, providing experimental evidence for comprehensive neurorestoration following SCI. Translational potential: This preclinical study demonstrated that subacute sequential hUC-MSCs transplantation is a promising therapeutic strategy for SCI. By improving both motor, emotional, and cognitive outcomes, it supports the concept of "brain-spinal co-repair" and provides a rationale for optimizing cell transplantation regimens to facilitate the clinical translation of hUC-MSC-based therapies for SCI.