Smith Sarah M, Limoli Charles L
Department of Radiation Oncology, University of California, Irvine, CA, 92697-2695, USA.
Curr Stem Cell Rep. 2017 Dec;3(4):342-347. doi: 10.1007/s40778-017-0105-5. Epub 2017 Oct 11.
To encapsulate past and current research efforts focused on stem cell transplantation strategies to resolve radiation-induced cognitive dysfunction.
Transplantation of human stem cells in the irradiated brain was first shown to resolve radiation-induced cognitive dysfunction in a landmark paper by Acharya ., appearing in PNAS in 2009. Since that time, work from the same laboratory as well as other groups have reported on the beneficial (as well as detrimental) effects of stem cell grafting after cranial radiation exposure. Improved learning and memory found many months after engraftment has since been associated with a preservation of host neuronal morphology, a suppression of neuroinflammation, improved myelination and increased cerebral blood flow. Interestingly, many (if not all) of these beneficial effects can be demonstrated by substituting stem cells with microvesicles derived from human stem cells during transplantation, thereby eliminating many of the more long-standing concerns related to immunorejection and teratoma formation.
Stem cell and microvesicle transplantation into the irradiated brain of rodents has uncovered some unexpected benefits that hold promise for ameliorating many of adverse neurocognitive complications associated with major cancer treatments. Properly developed, such approaches may provide much needed clinical recourse to millions of cancer survivors suffering from the unintended side effects of their cancer therapies.
总结过去和当前围绕干细胞移植策略以解决辐射诱发的认知功能障碍所开展的研究工作。
2009年发表于《美国国家科学院院刊》的一篇具有里程碑意义的论文中，阿查里亚等人首次证明，将人类干细胞移植到受辐射的大脑中可解决辐射诱发的认知功能障碍。自那时起，同一实验室以及其他团队的研究报告了颅骨辐射暴露后干细胞移植的有益（以及有害）影响。移植后数月发现学习和记忆能力得到改善，这与宿主神经元形态的保留、神经炎症的抑制、髓鞘形成的改善以及脑血流量的增加有关。有趣的是，在移植过程中用源自人类干细胞的微泡替代干细胞，许多（如果不是全部）这些有益效果都能得到证实，从而消除了许多与免疫排斥和畸胎瘤形成相关的长期担忧。
将干细胞和微泡移植到受辐射的啮齿动物大脑中发现了一些意想不到的益处，有望改善与主要癌症治疗相关的许多不良神经认知并发症。如果得到妥善发展，此类方法可能为数百万遭受癌症治疗意外副作用的癌症幸存者提供急需的临床解决方案。
