4.5 Article

INTRAVENOUS INJECTION OF UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELLS ATTENUATES REACTIVE GLIOSIS AND HYPOMYELINATION IN A NEONATAL INTRAVENTRICULAR HEMORRHAGE MODEL

Journal

NEUROSCIENCE
Volume 355, Issue -, Pages 175-187

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2017.05.006

Keywords

mesenchymal stromal cell; umbilical cord; intraventricular hemorrhage; cerebral palsy; brain-derived neurotrophic factor; Hepatocyte growth factor

Categories

Funding

  1. Japan Agency for Medical Research and Development/Ministry of Health, Labor and Welfare [16Abk0104010h0015]
  2. Ministry of Education, Culture, Sports, Science and Technology (JSPS KAKENHI) [JP26293251]
  3. Grants-in-Aid for Scientific Research [17J02535] Funding Source: KAKEN

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Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with alpha MEM medium supplemented with FBS or RM. A neonatal IVH mouse model at postnatal day 5 was generated by intraventricular injection of autologous blood, and mice were intravenously administered 1 x 10(5) UC-MSCs two days after IVH. Brain magnetic resonance imaging was performed at postnatal day 15, 22 and neurological behavioral measurements were performed at postnatal day 23, accompanied by histopathological analysis and cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs cultured with aMEM and RM met the criteria of MSCs and improved behavioral outcome of IVH mice. Moreover the RM group exhibited significant behavioral improvement compared to the control group. Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24 h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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