Abstract
INTRODUCTION: Hypoxic ischemic (HI) insults during pregnancy and birth can result in neurodevelopmental disorders, including cerebral palsy. We have previously shown that multiple doses of umbilical cord blood (UCB) cells are needed to effectively reduce long-term neuropathology and behavioural outcomes. Unfortunately, for multiple doses it is likely that UCB expansion will be required to increase the number of cells available for treatment. OBJECTIVES: In this study, we aimed to investigate the efficacy of expanded UCB derived CD34+ cells in modulating perinatal brain injury. METHODS: UCB derived CD34+ cells were expanded over a 14-day period using a previously optimised expansion protocol. HI injury was induced in postnatal day (P) 10 rats by left carotid artery ligation, followed by 90min hypoxia (8% oxygen). Pups were administered 1 million expanded UCB cells (eUCB) on P11, 13 and 20. Rats underwent extensive behavioural testing and post-mortem was performed on either P17 or P50 where tissue was collected for flow cytometry or immunohistochemistry analysis. RESULTS: After the 14-day expansion there was a ~800-fold increase in cell number with 70.7±2.18% CD34+ cells. Flow cytometry at P17 showed a significant increase in peripheral regulatory T-cells following eUCB administration (P=0.047). At P50, HI brain injury resulted in significant behavioural deficits and adverse neuropathologies. Multiple doses of eUCB significantly reduced microglial activation compared to HI in the cortex (P=0.02) and the hippocampus (P=0.018). DISCUSSION: Results from this study show for the first time that expanded UCB-derived CD34+ cells are a promising treatment option for perinatal brain injury as they have significant anti-inflammatory properties.