Abstract
BACKGROUND
White matter brain injury in preterm infants can induce neurodevelopmental deficits. Umbilical cord blood (UCB) cells demonstrate neuroprotective properties, but it is unknown whether cells obtained from preterm cord blood (PCB) vs. term cord blood (TCB) have similar efficacy. This study compared the ability of TCB vs. PCB cells to reduce white matter injury in preterm fetal sheep.
METHODS
Hypoxia–ischemia (HI) was induced in fetal sheep (0.7 gestation) by 25 min umbilical cord occlusion. Allogeneic UCB cells from term or preterm sheep, or saline, were administered to the fetus at 12 h after HI. The fetal brain was collected at 10-day post HI for assessment of white matter neuropathology.
RESULTS
HI (n=7) induced cell death and microglial activation and reduced total oligodendrocytes and CNPase+myelin protein in the periventricular white matter and internal capsule when compared with control (n=10). Administration of TCB or PCB cells normalized white matter density and reduced cell death and microgliosis (P<0.05). PCB prevented upregulation of plasma tumor necrosis factor (TNF)-a, whereas TCB increased anti-inflammatory interleukin (IL)-10 (P<0.05). TCB, but not PCB, reduced circulating oxidative stress.
CONCLUSIONS
TCB and PCB cells reduced preterm HI-induced white matter injury, primarily via anti-inflammatory actions. The secondary mechanisms of neuroprotection appear different following TCB vs. PCB administration.
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This work was made possible with financial support from Inner Wheel Australia, L.E.W. Carty Charitable Fund, Victorian Government Operational Infrastructure Support Program, an NHMRC Australia Project Grant (APP1081516) and ARC Future Fellowship to SLM.
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Li, J., Yawno, T., Sutherland, A. et al. Term vs. preterm cord blood cells for the prevention of preterm brain injury. Pediatr Res 82, 1030–1038 (2017). https://doi.org/10.1038/pr.2017.170
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DOI: https://doi.org/10.1038/pr.2017.170
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