Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19150-5. doi: 10.1073/pnas.0909293106. Epub 2009 Nov 9.
Cranial irradiation remains a frontline treatment for the control of tumor growth, and individuals surviving such treatments often manifest various degrees of cognitive dysfunction. Radiation-induced depletion of stem/precursor cell pools in the brain, particularly those residing in the neurogenic region of the hippocampus, is believed, in part, to be responsible for these often-unavoidable cognitive deficits. To explore the possibility of ameliorating radiation-induced cognitive impairment, athymic nude rats subjected to head only irradiation (10 Gy) were transplanted 2 days afterward with human embryonic stem cells (hESC) into the hippocampal formation and analyzed for stem cell survival, differentiation, and cognitive function. Animals receiving hESC transplantation exhibited superior performance on a hippocampal-dependent cognitive task 4 months postirradiation, compared to their irradiated surgical counterparts that did not receive hESCs. Significant stem cell survival was found at 1 and 4 months postirradiation, and transplanted cells showed robust migration to the subgranular zone throughout the dentate gyrus, exhibiting signs of neuron morphology within this neurogenic niche. These results demonstrate the capability to ameliorate radiation-induced normal tissue injury using hESCs, and suggest that such strategies may provide useful interventions for reducing the adverse effects of irradiation on cognition.
颅部照射仍然是控制肿瘤生长的一线治疗方法，接受此类治疗的患者通常会表现出不同程度的认知功能障碍。据认为，辐射导致脑内干细胞/前体细胞池（特别是那些位于海马神经发生区的细胞）耗竭，部分导致了这些不可避免的认知缺陷。为了探讨改善辐射诱导认知障碍的可能性，对接受头部照射（10Gy）的无胸腺裸鼠在 2 天后进行了人胚胎干细胞（hESC）移植，将其移植到海马区，并分析了干细胞的存活、分化和认知功能。与未接受 hESC 的照射手术对照组相比，接受 hESC 移植的动物在照射后 4 个月在海马依赖的认知任务中表现出更好的性能。在照射后 1 个月和 4 个月时发现了显著的干细胞存活，并且移植的细胞在整个齿状回的颗粒下区有很强的迁移能力，在这个神经发生龛中表现出神经元形态的迹象。这些结果表明，使用 hESC 可以改善辐射引起的正常组织损伤，并且表明这种策略可能为减少辐射对认知的不良影响提供有用的干预措施。
