Human neural stem cell transplantation ameliorates radiation-induced cognitive dysfunction.
Human neural stem cell transplantation ameliorates radiation-induced cognitive dysfunction.
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DOI：
10.1158/0008-5472.can-11-0027
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发表时间：
2011-07-15
期刊：
影响因子：
11.2
通讯作者：
Limoli CL
中科院分区：
文献类型：
--
作者：
Acharya MM;Christie LA;Lan ML;Giedzinski E;Fike JR;Rosi S;Limoli CL
颅脑放射治疗诱导认知的进行性和衰弱性下降，这可能部分是由神经干细胞的耗竭引起的。使用干细胞替代作为对抗辐射诱导的认知能力下降的策略的潜力通过照射无胸腺裸大鼠，2天后通过海马内移植人神经干细胞（hNSC）来解决。在照射后1个月和4个月评估认知表现、hNSC存活和表型命运的测量。移植hNSCs的辐照动物的认知功能下降明显低于辐照、假移植动物，并且与未辐照对照组的作用不可分割。无偏体视学显示，移植后1个月和4个月分别有23%和12%的移植细胞存活。移植的细胞广泛迁移，分化沿着神经胶质和神经元谱系，并表达活性调节的细胞因子相关蛋白（Arc），这表明他们的能力，功能整合到海马。这些数据表明，hNSCs提供了一个很有前途的策略，在功能上恢复辐射动物的认知。
Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days later by intrahippocampal transplantation with human neural stem cells (hNSC). Measures of cognitive performance, hNSC survival, and phenotypic fate were assessed at 1 and 4 months after irradiation. Irradiated animals engrafted with hNSCs showed significantly less decline in cognitive function than irradiated, sham-engrafted animals and acted indistinguishably from unirradiated controls. Unbiased stereology revealed that 23% and 12% of the engrafted cells survived 1 and 4 months after transplantation, respectively. Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus. These data show that hNSCs afford a promising strategy for functionally restoring cognition in irradiated animals.