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    Title: Human induced pluripotent stem cell-derived mesenchymal stem cell therapy effectively reduced brain infarct volume and preserved neurological function in rat after acute intracranial hemorrhage.
    Authors: 陳冠宏;Chen1, Kuan-Hung;林坤成;Lin, Kun-Chen;Christopher;Wallace, Christopher Glenn;李宜珍;Li, Yi-Chen;邵佩琳;Shao, Pei-Lin;蔣依吾;Chiang, John Y;宋沛勳;Sung, Pei-Hsun;葉漢根;Yip, Hon-Kan
    Contributors: 護理學系
    Keywords: Hemorrhagic stroke, iPSC-MSC, inflammation, oxidative stress
    Date: 2019-09
    Issue Date: 2020-08-20 15:50:44 (UTC+8)
    Publisher: 亞洲大學
    Abstract: We tested the hypothesis that human induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) therapy could effectively reduce brain-infarct volume (BIV) and improve neurological function in rat after acute intracranial hemorrhage (ICH) induced by a weight-drop device. Adult-male SD rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + hyaluronic acid (HA)/intracranial injection at 3 h after ICH), group 4 [ICH + HA + iPSC-MSC (1.2 × 106 cells/intracranial injection at 3 h after ICH)] and euthanized by day 28 after ICH procedure. In vitro study showed that hemorrhagic-brain tissue augmented protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/TNF-α/iNOS/IL-1β) in cultured neurons that were significantly inhibited by iPSC-MSC treatment (all P<0.001). By days 7 and 14 after ICH procedure, circulating inflammatory levels of TNF-α/IL-6/MPO expressed were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all P<0.0001). By day 14 after ICH procedure, neurological function and BIV expressed an opposite pattern, whereas protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/I-kB/TNF-α/iNOS/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved-caspase-2/PARP) in brain exhibited an identical pattern to circulating inflammation among the four groups (all P<0.001). Microscopy demonstrated that the number of vascular remodeling and GFAP+/53BP1+/γ-H2AX+ cells displayed an identical pattern of inflammation, whereas the NeuN+ cells displayed an opposite pattern of inflammation among the four groups (all P<0.001). In conclusion, iPSC-MSC therapy markedly reduced BIV and preserved neurological function mainly by inhibiting inflammatory/oxidative-stress generation.
    Relation: American Journal of Translational Research
    Appears in Collections:[Department of Nursing] Journal Article

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