How to prevent/remediate the neurodevelopmental disorders related to low birthweight in offspring rats exposed to mild intrauterine hypoperfusion

Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactive disorder and autism spectrum disorder, as well as cerebral palsy, for which no prophylactic treatment exists. Neuroinflammation in fetuses and neonates appears to be key in the emergence of NDDs. Meanwhile, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) exhibit immunomodulatory properties. Therefore, we hypothesized that systemic administration of UC-MSCs in the early postnatal period may attenuate neuroinflammation and thereby prevent the emergence of NDDs. We have developed a rat model of mild intrauterine hypoperfusion, which causes fetal growth restriction and pups are born with low birthweight. The low birthweight pups present many brain and behavioral impairments that I will describe. For the cell therapy study, we intravenously injected human UC-MSCs on postnatal day 1 (P1). UC-MSCs partially ameliorated behaviors and excitation-inhibition imbalance, while anti-inflammatory effects were not remarkable. I will present our recent data on the effects of MSC treatment, and it possible mechanisms of action throughout the gut microbiota.