Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericy- tic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vas- cular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compres- sion/contusion injury was induced at C7-T1 in adult female rats, followed by an intravenous tail vein infusion 1-hour post-SCI of (a) term-birth human umbilical cord perivascular cells (HUCPVCs); (b) first-trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24-hours or 10-weeks post-SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC-infused rats displayed improved (p < .05) grip strength com- pared with vehicle controls. However,onlyFTM HUCPVC-infusion ledtosignificant weight gain. All cell infusion treatments resulted in reduced glial scarring (p < .05). Cell infusion also led to increased axo- nal, myelin, and vascular densities (p < .05). Although post-traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long-term func- tional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI.