Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neonatal mortality and severe long-term neurological morbidity in infants born at term. Current treatment options for HIE are limited, but mesenchymal stem cell (MSC) therapy is an emerging and promising strategy. Our group has shown previously that intranasal administration of bone marrow-derived MSCs (bmMSCs) in a mouse model of neonatal HIE reduces infarct size by 40-50% and improves sensorimotor and cognitive outcome. The proposed mechanism of action of bmMSCs is that transplanted bmMSCs secrete different factors and therefore boost the endogenous regeneration of the injured brain by driving the differentiation of neural stem cells (NSCs) towards the neural cell fate.