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Grafted neural stem cells show lesion-specific migration in radiation-injured rat brains

机译:嫁接的神经干细胞在辐射损伤的大鼠大脑中显示出病变特异性迁移

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Neural stem cells (NSCs) exhibit preferential homing toward some types of brain lesion, but their migratory property during radiation brain injury (RBI) remains unexplored. Here, we use the superparamagnetic iron oxide (SPIO)-labeled magnetic resonance imaging (MRI) technology to determine the migration of transplanted NSCs in two partial RBI models in real time, created by administering 30–55 Gy of radiation to the right or posterior half of the adult rat brain. SPIO-labeled NSCs were stereotactically grafted into the uninjured side one week after RBI. The migration of SPIO-labeled NSCs in live radiation-injured brains was traced by MRI for up to 28 days after engraftment and quantified for their moving distances and speeds. A high labeling efficiency (>90%) was achieved by incubating NSCs with 100 μg ml ~(?1) of SPIO for 12–24 hours. Upon stereotactic transplantation into the healthy side of the brain, SPIO-labeled NSCs were distinctively detected as hypointense signals on T2-weighted images (T2WI), showed sustained survival for up to 4 weeks, and exhibited directional migration to the radiation-injured side of the brain with a speed of 86–127 μm per day. The moving kinetics of grafted NSCs displayed no difference in brains receiving a high (55 Gy) vs. moderate (45 Gy) dose of radiation, but was slower in the right RBI model than in the posterior RBI model. This study shows that NSCs can be effectively labeled by SPIO and traced in vivo by MRI, and that grafted NSCs exhibit directional migration toward RBI sites in a route-dependent but radiation dose-independent manner.
机译:神经干细胞(NSC)对某些类型的脑部病变表现出优先归巢,但在辐射性脑损伤(RBI)期间其迁移特性仍未开发。在这里,我们使用超顺磁性氧化铁(SPIO)标记的磁共振成像(MRI)技术来确定移植的NSC在两个局部RBI模型中的实时迁移,该模型是通过向右或向后管理30-55 Gy辐射而创建的成年大鼠大脑的一半。 SPIO标记的NSC在RBI一周后被立体定向​​移植到未受伤的一侧。植入后长达28天,MRI追踪了SPIO标记的NSC在放射性放射损伤的大脑中的迁移,并对其移动距离和速度进行了量化。通过将NSC与100μgml〜(?1)的SPIO孵育12-24小时,可以达到较高的标记效率(> 90%)。将立体定向移植到大脑的健康一侧后,在T2加权图像(T2WI)上将SPIO标记的NSCs作为低信号明显地检测到,显示出可持续的存活长达4周,并定向迁移到了受辐射损伤的一侧。大脑的速度为每天86–127μm。移植的NSC的运动动力学在接受高剂量(55 Gy)与中等剂量(45 Gy)辐射的大脑中没有差异,但是在右侧RBI模型中比在后RBI模型中慢。这项研究表明,NSCs可以被SPIO有效标记并通过MRI进行体内追踪,并且移植的NSCs会以途径依赖性但辐射剂量依赖性的方式向RBI位点方向迁移。

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