期刊
CELL TRANSPLANTATION
卷 25, 期 6, 页码 1131-1144出版社
SAGE PUBLICATIONS INC
DOI: 10.3727/096368915X689640
关键词
Intraventricular hemorrhage (IVH); Infant; Newborn; Mesenchymal stem cells (MSCs); Cell transplantation
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2014R1A1A3051220]
- Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea [A110445, HR14C0008]
- Samsung Biomedical Research Institute grant [SMX1150481]
- IN SUNG Foundation of Medical Research grant [CB28021]
We recently showed that intraventricular transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated posthemorrhagic hydrocephalus (PHH) and brain injury after severe intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this study was to optimize the timing of MSC transplantation for severe IVH. Severe IVH was induced by injecting 100 mu l of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). Human UCB-derived MSCs (1 x 10(5) cells in 10 mu l of normal saline) were transplanted intraventricularly under. stereotaxic guidance either early at P6 or late at P11. Serial brain MRIs and behavioral function tests, such as negative geotaxis and rotarod tests, were performed. At P32, brain tissue samples were obtained for histological and biochemical analyses. Intracerebroventricular transplantation of MSCs significantly attenuated the development of PHH, behavioral impairment, increased apoptosis and astrogliosis, reduced corpus callosum thickness and brain myelination, and upregulated inflammatory cytokines including interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) at P6 but not at P11 after induction of severe IVH. Intracerebroventricular transplantation of human UCB -derived MSCs attenuated PHH and brain injury after severe IVH in newborn rats in a time-dependent manner. Significant neuroprotection was only demonstrated when administered early at 2 days after induction but not late at 7 days after induction of severe IVH.
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