Moderate neuroprotection of combination cell therapy in fetal growth restricted newborns at postnatal day 10

Infants with fetal growth restriction (FGR) are at increased risk of adverse neurodevelopmental conditions, including motor, learning, and behavioral deficits. There are currently no treatments to protect the FGR newborn from lifelong neurological conditions. We have previously reported neuroprotective potential of a single dose of combined mesenchymal stromal cells and endothelial colony-forming cells (ECFCs) therapy, termed cECFC, isolated from healthy human term placenta, in treating brain injury in a preclinical model of FGR. We administered cECFCs to newborn FGR pigs and survived to postnatal day 4 (2-week human equivalence). We reported improved gray and white matter integrity, reduced glial-mediated inflammation and improved microvasculature. Here, we aimed to examine whether this novel therapy presented sustained efficacy in newborn pigs that survived to postnatal day 10 (1-month human equivalence). We determined a single dose of cECFC treatment affords moderate neuroprotective capacity in the cortex but limited efficacy in the periventricular white matter. We also report minimal modulation of the inflammatory environment, with ongoing glial activation observed in most regions examined. Our data suggest a diminution in efficacy of single-dose cECFC 10 days after administration. We propose multiple doses of cECFCs may be required to maintain neuroprotective capacity during early post-natal life in FGR newborns. Overall, these findings demonstrate the importance of extended pre-clinical studies to determine the efficacy of treatments prior to translation to clinical trials.