Human primed endothelial colony forming cells exert neuroprotective effects in the growth restricted newborn piglet

The fetal brain is particularly vulnerable to the detrimental effects of fetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure fetal mesenchymal stem cells and endothelial colony forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of these primed ECFCs (pECFC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using mesenchymal stromal cells alone. These results demonstrate pECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and act as a neuroprotectant. One Sentence Summary Stem cell treatment improves brain outcomes in the growth restricted newborn ### Competing Interest Statement The authors have declared no competing interest. * FGR : fetal growth restriction NG : normally grown NVU : neurovascular unit MSC : mesenchymal stem cells ECFC : endothelial colony forming cells pECFC : primed endothelial colony forming cells BBB : blood brain barrier UCB : umbilical cord blood IGWM : intragyral white matter SCWM : subcortical white matter PVWM : periventricular white matter GFAP : glial fibrillary protein Iba-1 : ionized binding protein-1 NeuN : neuronal nuclei MAP2 : microtubule-associated protein 2 IL-1β : interleukin-1β TNFα : tumor necrosis factorα PCR : polymerase chain reaction HIE : hypoxic-ischemic encephalopathy MRI : magnetic resonance imaging NF : neurofilament Olig2 : oligodendrocyte maker 2