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.


CONCLUSIONS
These results suggest that human UCB-derived MSCs are a promising therapeutic candidate for the treatment of severe perinatal brain injury including neonatal stroke.
Department of Pediatrics, Samsung Medical Center, Seoul, South Korea.
Eun Sun
ES
Kim
So Yoon
SY
Ahn
Geun Ho
GH
Im
Dong Kyung
DK
Sung
Ye Rim
YR
Park
Seo Hui
SH
Choi
Soo Jin
SJ
Choi
Yun Sil
YS
Chang
Wonil
W
Oh
Jung Hee
JH
Lee
Won Soon
WS
Park
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000517:prevention & control; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D020768:Middle Cerebral Artery / Q000473:pathology*; D051381:Rats