Transplantation of human dental pulp stem cells ameliorates brain damage following acute cerebral ischemia
Transplantation of human dental pulp stem cells ameliorates brain damage following acute cerebral ischemia
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DOI：
10.1016/j.biopha.2018.09.084
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发表时间：
2018-12-01
影响因子：
7.5
通讯作者：
Kimura, Kazumi
中科院分区：
文献类型：
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作者：
Nito, Chikako;Sowa, Kota;Kimura, Kazumi
目的：大量实验研究表明，细胞疗法，包括人牙髓干细胞（DPSC），是治疗缺血性脑损伤的一种有吸引力的策略。在此，我们检查了大鼠短暂大脑中动脉闭塞后静脉注射 DPSC 的效果。方法：雄性 Sprague-Dawley 大鼠接受短暂 90 分钟大脑中动脉闭塞。缺血再灌注后 0 小时或 3 小时通过股静脉给予 DPSC（1 x 10(6) 细胞）或载体。 PKH26是一种红色荧光细胞连接物，用于追踪大脑中的移植细胞。再灌注后24小时和72小时进行梗塞体积、神经功能缺损和免疫学分析。结果：PKH26阳性细胞在同侧比对侧半球更常见。再灌注后 0 小时移植的 DPSC 显着减少了梗塞体积，并在 24 小时和 72 小时恢复时逆转了运动缺陷。与赋形剂组相比，再灌注后 3 小时移植的 DPSC 在 24 小时和 72 小时恢复时也显着减少了梗塞体积并改善了运动功能。此外，再灌注后 72 小时，与对照组相比，DPSC 移植显着抑制小胶质细胞活化和促炎细胞因子表达。此外，DPSC 还可减轻皮质缺血边界区域的神经元变性。结论：再灌注后全身输送人 DPSC 可减少啮齿动物缺血模型中的缺血性损伤并改善功能恢复，具有临床相关的治疗窗。 DPSC 的神经保护作用可能与中风急性期神经炎症的调节有关。
Aims: Numerous experimental studies have shown that cellular therapy, including human dental pulp stem cells (DPSCs), is an attractive strategy for ischemic brain injury. Herein, we examined the effects of intravenous DPSC administration after transient middle cerebral artery occlusion in rats.Methods: Male Sprague-Dawley rats received a transient 90 min middle cerebral artery occlusion. DPSCs (1 x 10(6) cells) or vehicle were administered via the femoral vein at 0 h or 3 h after ischemia-reperfusion. PKH26, a red fluorescent cell linker, was used to track the transplanted cells in the brain. Infarct volume, neurological deficits, and immunological analyses were performed at 24 h and 72 h after reperfusion.Results: PKH26-positive cells were observed more frequently in the ipsilateral than the contralateral hemisphere. DPSCs transplanted at 0 h after reperfusion significantly reduced infarct volume and reversed motor deficits at 24 h and 72 h recovery. DPSCs transplanted at 3 h after reperfusion also significantly reduced infarct volume and improved motor function compared with vehicle groups at 24 h and 72 h recovery. Further, DPSC transplantation significantly inhibited microglial activation and pro-inflammatory cytokine expression compared with controls at 72 h after reperfusion. Moreover, DPSCs attenuated neuronal degeneration in the cortical ischemic boundary area.Conclusions: Systemic delivery of human DPSCs after reperfusion reduced ischemic damage and improved functional recovery in a rodent ischemia model, with a clinically relevant therapeutic window. The neuroprotective action of DPSCs may relate to the modulation of neuroinflammation during the acute phase of stroke.