Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight

Abstract

Abstract 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. Neuroinflammation in fetuses and neonates plays a major pathogenic role in NDDs. Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have immunomodulatory properties. LBW pups born to dams subjected to mild intrauterine hypoperfusion and pups born to sham-treated dams, received intravenous administration of either human UC-MSCs (1 × 105 cells) or a vehicle on postnatal day 1 (P1). Rats in the LBW-vehicle group exhibited significantly lesser decrease in the monosynaptic response with increased frequency of stimulation to the spinal cord preparation from P4 to P6, suggesting hyperexcitability, which was improved by UC-MSC treatment. Three-chamber sociability tests at 7 weeks of age showed that only males in the LBW-vehicle group exhibited disturbed sociability, which was ameliorated by UC-MSC treatment. Other parameters, including those determined via open-field tests, were not improved by UC-MSC treatment. Serum or cerebrospinal fluid levels of pro-inflammatory cytokines were not elevated in the LBW-vehicle group, and the effects of UC-MSC treatment on inflammation were unclear. In conclusion, UC-MSC treatment may prevent the development of NDDs.