Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury

Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury
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DOI:
10.3727/096368916x694391
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发表时间:
2017-01-01
影响因子:
3.3
通讯作者:
Kim, Eun-Cheol
Kim, Eun-Cheol
中科院分区:
医学4区
文献类型:
--
作者:
Song, Miyeoun;Lee, Jae-Hyung;Kim, Eun-Cheol

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我们比较了移植人牙髓干细胞(HDPSCs)和人骨髓间充质干细胞(HBM-MSCs)在大鼠卒中模型和体外缺血模型中的治疗效果和机制。大鼠大脑中动脉闭塞(MCAO)后24 h静脉注射hDPSC或HBM-MSCs后,两组大鼠的功能恢复均有改善,脑梗塞体积缩小,但hDPSC组较HBM-MSC组脑梗塞体积缩小更明显。HDPSC组内皮细胞标志物阳性面积大于HBM-MSC组。与HBM-MSCs相比,hDPSCs可显著减少MCAO诱导的GFAP(+)/Nestin(+)和GFAP(+)/Musashi-1(+)细胞的反应性胶质增生。体外实验结果证实,hDPSCs在缺氧缺糖损伤的人脑星形胶质细胞(HAS)中表现出比HBM-MSCs更好的神经保护、迁移和体外血管生成作用。用RNA测序技术对hDPSC-和HBM-MSC体外处理缺氧损伤的HAS进行了全面的比较生物信息学分析。在基因本体论和KEGG通路分析中,hDPSC处理组的重要通路是MAPK和转化生长因子-β信号通路。因此,hDPSCs可能是一种比HBM-MSCs更好的治疗缺血性中风的细胞来源。
We compared the therapeutic effects and mechanism of transplanted human dental pulp stem cells (hDPSCs) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a rat stroke model and an in vitro model of ischemia. Rats were intravenously injected with hDPSCs or hBM-MSCs 24 h after middle cerebral artery occlusion (MCAo), and both groups showed improved functional recovery and reduced infarct volume versus control rats, but the hDPSC group showed greater reduction in infarct volume than the hBM-MSC group. The positive area for the endothelial cell marker was greater in the lesion boundary areas in the hDPSC group than in the hBM-MSC group. Administration of hDPSCs to rats with stroke significantly decreased reactive gliosis, as evidenced by the attenuation of MCAo-induced GFAP(+)/nestin(+) and GFAP(+)/Musashi-1(+) cells, compared with hBM-MSCs. In vivo findings were confirmed by in vitro data illustrating that hDPSCs showed superior neuroprotective, migratory, and in vitro angiogenic effects in oxygen-glucose deprivation (OGD)injured human astrocytes (hAs) versus hBM-MSCs. Comprehensive comparative bioinformatics analyses from hDPSC-and hBM-MSC-treated in vitro OGD-injured hAs were examined by RNA sequencing technology. In gene ontology and KEGG pathway analyses, significant pathways in the hDPSC-treated group were the MAPK and TGF-beta signaling pathways. Thus, hDPSCs may be a better cell therapy source for ischemic stroke than hBM-MSCs.