Fetal and Neonatal Stem Cells Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury

Spinal cord injury (SCI) is a life-threatening conditionwithmultifacetedcomplications andlimitedtreat- ment options. In SCI, the initial physical trauma is closely followed by a series of secondary events, in- cluding inflammation and blood spinal cord barrier (BSCB) disruption,which further exacerbate injury. This secondary pathology is partiallymediated by the systemic immune response to trauma, in which cytokine production leads to the recruitment/activation of inflammatory cells. Because early intrave- nousdelivery ofmesenchymal stromal cells (MSCs)hasbeenshowntomitigateinflammationinvarious models of neurologic disease, this study aimed to assess these effects in a rat model of SCI (C7-T1, 35- gram clip compression) using human brain-derived stromal cells. Quantitative polymerase chain reac- tionforahuman-specificDNAsequencewasusedtoassesscellbiodistribution/clearanceandconfirmed that only a small proportion (approximately 0.001%–0.002%) of cells are delivered to the spinal cord, withthemajorityresidinginthelung, liver,andspleen. Intriguingly, althoughcellpopulationsdrastically declined in all aforementioned organs, there remained a persistent population in the spleen at 7 days. Furthermore, the cell infusion significantly increased splenic and circulating levels of interleukin-10— a potent anti-inflammatory cytokine. Through this suppression of the systemic inflammatory re- sponse, the cells also reduced acute spinal cord BSCB permeability, hemorrhage, and lesion volume. These early effects further translated into enhanced functional recovery and tissue sparing 10 weeks after SCI. This work demonstrates an exciting therapeutic approach whereby aminimally invasive cell-transplantation procedure can effectively reduce secondary damage after SCI throughsystemic immunomodulation.