Human umbilical cord blood-derived mesenchymal stem cell transplantation attenuates severe brain injury by permanent middle cerebral artery occlusion in newborn rats

Background:Severe brain injury induced by neonatal stroke causes significant mortality and disability, and effective therapies are currently lacking. We hypothesized that human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) can attenuate severe brain injury induced by permanent middle cerebral artery occlusion (MCAO) in rat pups.Methods:After confirming severe brain injury involving more than 50% of the ipsilateral hemisphere volume at 1 h after MCAO using diffusion-weighted magnetic resonance imaging (MRI) in postnatal day (P)10 rats, human UCB-derived MSCs were transplanted intraventricularly. The brain MRI was evaluated periodically up to 28 d after MCAO (P38). Sensorimotor function and histology in the peri-infarct tissues were evaluated at the end of the experiment.Results:Severe brain injury induced by permanent MCAO resulted in decreased survival and body weight gain, increased brain infarct volume as measured by MRI, impaired functional tests such as the rotarod and cylinder test, and histologic abnormalities such as increased terminal deoxynucleotidyl transferase nick-end labeling, reactive microglial marker, and glial fibrillary acidic protein-positive cells in the penumbra. All of these abnormalities were significantly improved by MSC transplantation 6 h after MCAO.Conclusion: These results suggest that human UCB-derived MSCs are a promising therapeutic candidate for the treatment of severe perinatal brain injury including neonatal stroke.