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

Abstract Introduction Preterm infants are at high risk for white matterinjury 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 matterinjury. Methods 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. Results HI induced white matterinjury, as indicated by a reduction in CNPase-positive myelin fiber density. HI also induced microglial activation (Iba-1) in the periventricular white matterand internal capsule( P P P Conclusions UCB-derived MSC therapy preserved white matterbrain structure following preterm HI, mediated by a suppression of microglial activation, promotion of macrophage migration and acceleration of self-repair within the preterm brain. UCB-derived MSC are neuroprotective, acting via peripheral and cerebral anti-inflammatory and immunomodulatory mechanisms.