Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke.
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.
Department 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.
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Tsuji
Department 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.
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Taguchi
Department 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.
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Ohshima
Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, 2-2, Minami-machi, Minatojima, Chuo-ku, Kobe 650-0047, Japan.
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Kasahara
Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
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Sato
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
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Tsuda
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
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Otani
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
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Yamahara
Department 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.
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Ihara
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
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Harada-Shiba
Department 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.
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Ikeda
Laboratory 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.
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Matsuyama
D061605:Administration, Intravenous; D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D045442:Rotarod Performance Test; D020521:Stroke / Q000628:therapy*
D018952:Antigens, CD34
CD34(+) cell; brain injury; cell-based therapy; neonatal encephalopathy; neonatal stroke; umbilical cord blood