Introduction: Severe birth asphyxia can result in significant brain inflammation and injury, leading to cerebral palsy in surviving infants. The umbilical cord blood mononuclear layer contain populations of cells that possess anti-inflammatory properties that have the potential to reduce inflammation and ameliorate neuropathology caused by birth asphyxia.
Methods: Birth asphyxia was induced via umbilical cord occlusion (UCO), before caesarean section delivery, in 20 term lambs (141 days gestation). Eight lambs were delivered by caesarean section without UCO (Controls). Umbilical cord blood (CB) was obtained at delivery. The mononuclear layer was isolated and labeled with fluorescing iron nanoparticles. A representative sample was analysed for cell type by FACS. Autologous cord blood (UCO+CB; 100±20million, n=8) was administered 12 hours after delivery. Magnetic resonance spectroscopy (MRS) was undertaken at 12 and 72 hours, lambs were euthanased at 72 hours for organ collection and histological analysis.
Results and Discussion: Cord blood contained mixed populations of MSCs and EPCs. Metabolic derangement (N-acetyl aspartate:lactate ratio), determined by MRS, was increased in UCO lambs at 12h and 72 hours (12h:0.20±0.05; 72h:0.3±0.19) compared to control (12h:0.1±0.07; 72h:0.1±0.06). Following CB administration, UCO+CB animals were not different from control (72h:0.09±0.02). Iron labeled CB cells were not visualized radiologically. Histological analysis showed fluorescing CB widely distributed within the cortex, white matter and deep grey matter of UCO+CB brains. Macrophage and microglia activation (lectin peroxidase) and neuronal cell death was significantly increased in brains of UCO, compared to control lambs, but was reduced to control levels in UCO+CB lambs, p=0.01.
Conclusion: Term lamb CB contains populations of EPCs and MSCs. Administration of autologous CB to newborn lambs following severe birth asphyxia improves behavioural and biophysical outcomes. We are now investigating which individual components of cord blood are responsible for the efficacious effects observed.