Cord blood-derived cell therapies for preterm brain injury

Abstract

Preterm birth, defined as delivery before 37 weeks of gestation, remains a leading contributor to neonatal morbidity and long-term neurodevelopmental impairments. Brain injuries such as intraventricular haemorrhage, white matter injury and hypoxic-ischemic encephalopathy are common in this population and are mediated by overlapping pathophysiological mechanisms including inflammation, cerebrovascular immaturity, cell death and impaired repair. Current therapeutic options for these conditions are limited and are largely supportive. Umbilical cord blood (UCB)-derived cell therapy has emerged as a novel strategy to target these shared pathophysiological pathways. UCB contains diverse cell types—hematopoietic stem cells, mesenchymal stromal cells, endothelial progenitor cells and regulatory T cells—with regenerative, immunomodulatory and neuroprotective properties. Preclinical studies in rodent and limited large-animal models show consistent benefits of UCB therapy, including attenuation of neuroinflammation, reduced apoptosis, promotion of oligodendrocyte maturation and improved functional outcomes. However, variability in model design and lack of long-term endpoints hinder clinical translation. Clinical research into cord blood-derived therapies for preterm brain injury is still in its early stages, with most studies to date focused on feasibility and safety rather than efficacy. While preventative approaches have dominated, therapeutic trials for infants with established brain injury remain limited. Small case series suggest potential benefits in intraventricular haemorrhage, but other injury types, such as hypoxic-ischemic encephalopathy, stroke, or cerebellar haemorrhage, remain largely unexplored in the preterm population. Recent studies using reinfusion of a preterm infant's own cord blood derived cells show promising safety and early signs of reduced risk for conditions like cerebral palsy. Larger efficacy trials are now underway, including those targeting severe, established preterm brain injuries, marking a significant step toward clinical application.