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.
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.
Authors: Nienke Wagenaar; Caroline G M de Theije; Linda S de Vries; Floris Groenendaal; Manon J N L Benders; Cora H A Nijboer Journal: Pediatr Res Date: 2017-11-01 Impact factor: 3.756
Authors: So Yoon Ahn; Yun Sil Chang; Dong Kyung Sung; Se In Sung; Jee-Yin Ahn; Won Soon Park Journal: Cell Transplant Date: 2016-08-16 Impact factor: 4.064
Authors: Koteswara Rao Nalamolu; Ishwarya Venkatesh; Adithya Mohandass; Jeffrey D Klopfenstein; David M Pinson; David Z Wang; Adinarayana Kunamneni; Krishna Kumar Veeravalli Journal: Neuromolecular Med Date: 2019-05-10 Impact factor: 3.843
Authors: Jun Lei; Wance Firdaus; Jason M Rosenzweig; Shorouq Alrebh; Ahmed Bakhshwin; Talaibek Borbiev; Ali Fatemi; Karin Blakemore; Michael V Johnston; Irina Burd Journal: Am J Obstet Gynecol Date: 2014-12-30 Impact factor: 8.661
Authors: Cindy T J van Velthoven; R Ann Sheldon; Annemieke Kavelaars; Nikita Derugin; Zinaida S Vexler; Hanneke L D M Willemen; Mirjam Maas; Cobi J Heijnen; Donna M Ferriero Journal: Stroke Date: 2013-03-28 Impact factor: 7.914