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首页> 外文期刊>American Journal of Translational Research >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
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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

机译：人诱导多能干细胞衍生的间充质干细胞疗法有效地降低了急性颅内出血后大鼠大鼠脑梗死体积和保存神经功能

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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 × 10 6 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 P0.001). 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 P0.0001). 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 P0.001). 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 P0.001). In conclusion, iPSC-MSC therapy markedly reduced BIV and preserved neurological function mainly by inhibiting inflammatory/oxidative-stress generation.
机译：我们测试了人诱导的多能干细胞衍生的间充质干细胞（IPSC-MSC）治疗的假设可以有效地降低脑梗塞体积（BIV），并在急性颅内出血（ICH）诱导后提高大鼠的神经功能设备。成人 - 雄性SD大鼠（n = 40）同等分为第1组（假手术控制），第2组（ICH），第3组（ICH +透明质酸（HA）/ ICH后3小时的颅内注射），组4 [ICH + HA + IPSC-MSC（1.2×10 6个细胞/ ICH之后的3小时内注射）]并在ICH程序后第二天被安乐死。体外研究表明，在IPSC显着抑制的培养神经元中，出血性 - 脑组织增强蛋白表达（HMGB1 / MyD88 / TLR-4 / TLR-2 / NF-κB/ TNF-α/ InOS / IL-1β） -MSC处理（所有P <0.001）。在ICH过程之后的第7和14天，表达TNF-α/ IL-6 / MPO的循环炎症水平在第1组中最低，第2组中最高，并且在第4组中显着降低（所有P <0.0001）。在第14天，在ICH程序后，神经功能和BIV表达相反的模式，而炎症的蛋白表达（HMGB1 / MYD88 / TLR-4 / TLR-2 / NF-κB/ I-KB / TNF-α/ INOS / IL- 1β/ mmp-9），氧化应激（NOx-1 / NOx-2 /氧化蛋白）和脑中的凋亡（线粒体 - BAX /切割Caspase-2 / PARP）表现出与四组中循环炎症相同的模式（所有p＆ 0.001）。显微镜证明血管重塑和GFAP + / 53bp1 + /γ-H2AX +细胞的数量显示出相同的炎症模式，而Neun +细胞在四组中显示出相反的炎症模式（所有P <0.001）。总之，IPSC-MSC治疗主要通过抑制炎症/氧化应激产生，显着降低了BIV和保存的神经功能功能。

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