Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats
Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats
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DOI：
10.2176/nmc.oa.2019-0186
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发表时间：
2020-02-01
影响因子：
1.9
通讯作者：
Kurisu, Kaoru
中科院分区：
文献类型：
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作者：
Oshita, Jumpei;Okazaki, Takahito;Kurisu, Kaoru
以人髂骨间充质干细胞(HiMSCs)为对照，分析了人颅骨间充质干细胞(HcMSCs)在缺血性卒中模型大鼠体内的细胞特性、神经保护作用及移植效果。分析神经营养因子脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)在两种MSCs中的表达。分别于大鼠大脑中动脉闭塞(MCAO)后3h或2 4h静脉注射hh MSCs或hcMSCs，并进行神经功能评分。观察神经母细胞瘤-神经胶质瘤杂交瘤细胞(NG108-15)氧化应激或炎症应激3、24 h后的存活率，以及hcMSCs或hcMSCs条件培养液对氧化应激或炎症应激暴露3、24 h的NG108-15细胞的神经保护作用。HcMSCs中BDNF和VEGF的表达高于hcMSCs。MCAO后3h移植hcMSCs组较对照组和hcMSCs组功能明显恢复。应激后24 h的NG108-15细胞存活率低于应激3 h。与hcMSCs-CM共培养的NG108-15细胞氧化应激或炎症应激3h后的存活率明显高于对照组。我们的结果提示，缺血性卒中早期hcMSCs移植可抑制残留神经细胞的损伤，并通过强烈表达神经营养因子而导致功能恢复。这是第一个显示hcMSCs移植后缺血性卒中后功能恢复的报告。
We analyzed the cell characteristics, neuroprotective, and transplantation effects of human cranial bone-derived mesenchymal stem cells (hcMSCs) in ischemic stroke model rats compared with human iliac bone-derived mesenchymal stem cells (hiMSCs). The expressions of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) as neurotrophic factors were analyzed in both MSCs. hiMSCs or hcMSCs were intravenously administered into ischemic stroke model rats at 3 or 24 h after middle cerebral artery occlusion (MCAO) and neurological function was evaluated. The survival rate of neuroblastoma x glioma hybrid cells (NG108-15) after 3 or 24 h oxidative or inflammatory stress and the neuroprotective effects of hiMSCs or hcMSCs-conditioned medium (CM) on 3 or 24 h oxidative or inflammatory stress-exposed NG108-15 cells were analyzed. The expressions of BDNF and VEGF were higher in hcMSCs than in hiMSCs. hcMSCs transplantation at 3 h after MCAO resulted in significant functional recovery compared with that in the hiMSCs or control group. The survival rate of stress-exposed NG108-15 was lower after 24 h stress than after 3 h stress. The survival rates of NG108-15 cells cultured with hcMSCs-CM after 3 h oxidative or inflammatory stress were significantly higher than in the control group. Our results suggest that hcMSCs transplantation in the early stage of ischemic stroke suppresses the damage of residual nerve cells and leads to functional recovery through the strong expressions of neurotrophic factors. This is the first report demonstrating a functional recovery effect after ischemic stroke following hcMSCs transplantation.