Department of Neurosurgery, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1136, New York, NY 10029, USA.
Neuro Oncol. 2012 Mar;14(3):256-65. doi: 10.1093/neuonc/nor204. Epub 2011 Dec 13.
Stem cells have generated great interest in the past decade as potential tools for cell-based treatment of human high-grade gliomas. Thus far, 3 types of stem cells have been tested as vehicles for various therapeutic agents: embryonic, neural, and mesenchymal. The types of therapeutic approaches and/or agents examined in the context of stem cell-based delivery include cytokines, enzyme/prodrug suicide combinations, viral particles, matrix metalloproteinases, and antibodies. Each strategy has specific advantages and disadvantages. Irrespective of the source and/or type of stem cell, there are several areas of concern for their translation to the clinical setting, such as migration in the adult human brain, potential teratogenesis, immune rejection, and regulatory and ethical issues. Nonetheless, a clinical trial is under way using neural stem cell-based delivery of an enzyme/prodrug suicide combination for recurrent high-grade glioma. A proposed future direction could encompass the use of stem cells as vehicles for delivery of agents targeting glioma stem cells, which have been implicated in the resistance of high-grade glioma to treatment. Overall, stem cells are providing an unprecedented opportunity for cell-based approaches in the treatment of high-grade gliomas, which have a persistently dismal prognosis and mandate a continued search for therapeutic options.
在过去的十年中,干细胞作为人类高级别神经胶质瘤基于细胞治疗的潜在工具引起了极大的兴趣。迄今为止,已经测试了 3 种类型的干细胞作为各种治疗剂的载体:胚胎干细胞、神经干细胞和间充质干细胞。在基于干细胞传递的背景下,检查了包括细胞因子、酶/前药自杀组合、病毒颗粒、基质金属蛋白酶和抗体在内的各种治疗方法和/或药物。每种策略都有其特定的优点和缺点。无论干细胞的来源和/或类型如何,将其转化为临床环境都存在几个需要关注的问题,例如在成人脑中的迁移、潜在的致畸性、免疫排斥和监管及伦理问题。尽管如此,一项使用神经干细胞传递酶/前药自杀组合治疗复发性高级别神经胶质瘤的临床试验正在进行中。未来的一个提议方向可能包括将干细胞用作载体,以传递针对神经胶质瘤干细胞的药物,神经胶质瘤干细胞被认为是高级别神经胶质瘤对治疗产生抗性的原因之一。总的来说,干细胞为治疗高级别神经胶质瘤提供了前所未有的基于细胞的治疗方法的机会,高级别神经胶质瘤的预后一直很糟糕,需要继续寻找治疗选择。