Neonatal Mesenchymal Stromal Cell Therapy for Neuroprotection After Cardiopulmonary Bypass in Neonatal Swine

BACKGROUND Neonates undergoing surgery for congenital heart disease are at risk for neurologic injury, often related to neuroinflammation triggered by cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Neonatal mesenchymal stem cells (nMSCs), which possess strong immunomodulatory properties, may help mitigate this injury. METHODS In a neonatal swine model, thirteen piglets were randomized to sham, placebo, or nMSC treatment groups and underwent CPB with 60 minutes of DHCA, followed by administration of saline or 2 million cells/kg of nMSCs via the aortic cannula. RESULTS Six hours later, brain tissue analysis demonstrated that nMSC-treated animals had significantly reduced astrocyte and microglial activation, increased neuronal survival, and decreased apoptosis in the frontal lobe and brainstem compared with placebo. CONCLUSIONS These findings suggest that systemic delivery of nMSCs may reduce acute neuroinflammation and neuronal injury after CPB, supporting their potential role as a neuroprotective therapy during neonatal cardiac surgery.