**5. Future challenges for translation of umbilical cord blood therapies**

Almost all available evidence supports that UCB cell therapy provides neuroprotective and/ or neuroregenerative benefits in response to perinatal brain injury and established cerebral palsy. There do, however, remain a number of important questions around the *best practice* treatment with UCB cells to provide optimized outcomes for infants with perinatal brain injury. These questions are principally centered around whether whole cord blood (mononuclear cells) provides the best strategy, or whether individual cells (or combinations or cells) from cord blood should be expanded and subsequently administered to improve cell yield. Using this approach, cell therapy could be individualized depending on the pregnancy or birth complication. It is also not yet known what dose of cells is optimal, and when the cells should be administered relative to insult and diagnosis to provide the best outcome. All of these questions are best answered using animal models of chorioamnionitis, preterm birth, fetal growth restriction or birth asphyxia. A critical aim of designing novel therapies for perinatal brain injury is extending the treatment window so that cell therapy could be utilized for days to weeks after birth, not just within the 6 h of birth, as is necessary for hypothermia commencement in newborns with hypoxic ischemic encephalopathy. Ideally, cell therapy must be effective at mediating a spectrum of adverse events that occur within the perinatal brain, such as reducing glial scar formation, inflammation and neuronal cell death. In this review, we reveal that many cells derived from UCB have the potential to suppress inflammation and reduce brain injury when they are administered within 3-day post-injury. These results are encouraging, but it is important to appreciate that a successful and effective cell therapy will combine anti-inflammatory and neuroprotective abilities that will allow the ultimate goal of novel therapies for cerebral palsy, permitting a longer therapeutic window.
