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.