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

• Tsuji Masahiro
• Mukai Takeo
• Sato Yoshiaki
• Azuma Yasue
• Yamamoto Saki
• Cayetanot Florence
• Bodineau Laurence
• Onoda Atsuto
• Nagamura-Inoue Tokiko
• Coq Jacques-Olivier

Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attentiondeficit/hyperactive disorder and autism spectrum disorder, as well as cerebral palsy, for which no prophylactic measure exists. Neuroinflammation in fetuses and neonates plays a major pathogenic role in 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. The LBW pups born to dams subjected to mild intrauterine hypoperfusion exhibited a significantly lesser decrease in the monosynaptic response with increased frequency of stimulation to the spinal cord preparation from postnatal day 4 (P4) to P6, suggesting hyperexcitability, which was improved by intravenous administration of human UC-MSCs (1 × 10 5 cells) on P1. Three-chamber sociability tests at adolescence revealed that only LBW males exhibited disturbed sociability, which tended to be ameliorated by UC-MSC treatment. Other parameters, including those determined via open-field tests, were not significantly improved by UC-MSC treatment. Serum or cerebrospinal fluid levels of pro-inflammatory cytokines were not elevated in the LBW pups, and UC-MSC treatment did not decrease these levels. In conclusion, although UC-MSC treatment prevents hyperexcitability in LBW pups, beneficial effects for NDDs are marginal.