UMBILICAL CORD‑DERIVED MESENCHYMAL STROMAL CELL THERAPY PREVENTS THE DEVELOPMENT OF NEURODEVELOPMENTAL DISORDERS RELATED TO LOW BIRTH WEIGHT IN RATS

Low birthweight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attention deficit/hyperactivity disorder and autism spectrum disorder, as well as cerebral palsy, with no current prophylactic treatment. Neuroinflammation in fetuses and neonates is a key factor in NDD emergence. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) exert immunomodulatory and anti-inflammatory properties, offering potential therapeutic benefits. We developed a rat model of LBW based on mild intrauterine hypoperfusion (MIUH), which induced LBW and NDDs. Compared to sham-controls, MIUH-LBW rats exhibited persistent body weight reduction, decreased hippocampal neuronal density, spinal cord hyperexcitability, delayed sensorimotor reflexes, impaired sociability and hyperactivity, increased disinhibtion behaviors, and elevated levels of pro-inflammatory cytokines. Therefore, we hypothesized that systemic administration of UC-MSCs in the early postnatal period may attenuate neuroinflammation and thereby prevent the emergence of NDDs. Compared to LBW rats with vehicle, LBW rats treated early with UC-MSCs showed normalized gain of body weight, restored hippocampal neuronal density, normalized spinal cord excitability, improved sensorimotor reflexes, relative sociability improvement, reduced disinhibition, and decreased levels of pro-inflammatory cytokines. Thus, early UC-MSC treatment reduced hyperexcitability, improved executive functions, and decreased inflammation in LBW rats, suggesting a strong potential for future clinical translation. This work was supported by The Waterloo Foundation, the International joint Research Program of IMSUT, The Ambassade of France in Japan, Aix-Marseille Université and Derci CNRS.