Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development against hypoxia-ischemia

Preterm infants are at high risk for white matter injury and subsequent neurodevelopmental impairments. Mesenchymal stem/stromal cells (MSC) have anti-inflammatory/immunomodulatory actions and are of interest for neural repair in adults and newborns. This study examined the neuroprotective effects of allogeneic MSC, derived from preterm umbilical cord blood (UCB), in a preterm sheep model of white matter injury. Quad-lineage differentiation, clonogenicity and self-renewal ability of UCB-derived MSC were confirmed. Chronically instrumented fetal sheep (0.7 gestation) received either 25 min hypoxia-ischemia (HI) to induce preterm brain injury, or sham-HI. Ten million MSC, or saline, were administered iv to fetuses at 12 h after HI. Fetal brains were collected 10d after HI for histopathology and immunocytochemistry. HI induced white matter injury, as indicated by a reduction in CNPase-positive myelin fiber density. HI also induced microglial activation (Iba-1) in the periventricular white matter and internal capsule (P