Baulch Janet E, Acharya Munjal M, Allen Barrett D, Ru Ning, Chmielewski Nicole N, Martirosian Vahan, Giedzinski Erich, Syage Amber, Park Audrey L, Benke Sarah N, Parihar Vipan K, Limoli Charles L
Department of Radiation Oncology, University of California, Irvine, CA 92697-2695.
Department of Radiation Oncology, University of California, Irvine, CA 92697-2695
Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4836-41. doi: 10.1073/pnas.1521668113. Epub 2016 Apr 4.
Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment.
癌症幸存者在应对疾病复发以及放疗和化疗治疗方案带来的众多正常组织并发症时面临各种挑战。对于因控制中枢神经系统恶性肿瘤而接受颅脑照射的患者，进行性且使人衰弱的认知功能障碍仍然是迫切未得到满足的医疗需求。尽管这个问题已被认识数十年，但几乎没有令人满意的长期解决方案来解决放疗这种严重的意外副作用。我们实验室过去的研究表明，人神经干细胞（hNSC）移植到受照射的大脑中具有神经认知益处，其中hNSC的海马内移植改善了辐射诱导的认知缺陷。使用类似的策略，据我们所知，我们现在首次提供证据表明，hNSC分泌的微泡进行颅脑移植在仅头部照射后能提供类似的神经保护表型。在接受照射1个月后发现的基于皮质和海马的缺陷在接受微泡颅脑移植的动物中完全得到解决。发现微泡治疗可减轻神经炎症并在大脑的不同区域保留宿主神经元形态。这些数据表明，微泡的神经保护特性通过一种营养支持机制起作用，该机制可减轻炎症并保留受照射微环境的结构完整性。
