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Neuroscience. 2014 Mar 28;263:148-58. doi: 10.1016/j.neuroscience.2014.01.018. Epub 2014 Jan 18.

Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke.

Author information

  • 1Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan. Electronic address: tsuji.masahiro.ri@ncvc.go.jp.
  • 2Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan; Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, 2-2, Minami-machi, Minatojima, Chuo-ku, Kobe 650-0047, Japan. Electronic address: taguchi@fbri.org.
  • 3Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan. Electronic address: oshima.makiko.ri@ncvc.go.jp.
  • 4Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, 2-2, Minami-machi, Minatojima, Chuo-ku, Kobe 650-0047, Japan.
  • 5Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
  • 6Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
  • 7Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan; Department of Neurology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
  • 8Department of Obstetrics and Gynecology, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan. Electronic address: t-ikeda@clin.medic.mie-u.ac.jp.
  • 9Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Science, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: tomohiro@hyo-med.ac.jp.

Abstract

Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. However, all of the studies examined the effects of administering either the UCB mononuclear cell fraction or UCB-derived mesenchymal stem cells in neonatal rat models. The objective of this study was to examine the effects of human UCB CD34(+) cells (hematopoietic stem cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours after MCAO, human UCB CD34(+) cells (1×10(5)cells) were injected intravenously into the mice. The area in which cerebral blood flow (CBF) was maintained was temporarily larger in the cell-treated group than in the phosphate-buffered saline (PBS)-treated group at 24h after treatment. With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34(+) cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area.

Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

CD34(+) cell; brain injury; cell-based therapy; neonatal encephalopathy; neonatal stroke; umbilical cord blood

PMID:
24444827
[PubMed - indexed for MEDLINE]
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