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Stem cells as therapeutic vehicles for the treatment of high-grade gliomas

机译:干细胞作为治疗高级神经胶质瘤的治疗载体

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摘要

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.
机译:在过去的十年中,干细胞作为基于细胞的人类高级神经胶质瘤治疗的潜在工具引起了极大的兴趣。迄今为止,已经测试了三种类型的干细胞作为各种治疗剂的载体:胚胎,神经和间充质。在基于干细胞的递送中检查的治疗方法和/或药物类型包括细胞因子,酶/前药自杀组合,病毒颗粒,基质金属蛋白酶和抗体。每种策略都有其特定的优点和缺点。不论干细胞的来源和/或类型如何,其向临床环境的转化都有几个方面值得关注,例如成年人脑中的迁移,潜在的致畸作用,免疫排斥以及调节和伦理问题。尽管如此,一项临床试验正在使用基于神经干细胞的酶/前药自杀联合治疗复发性高级别神经胶质瘤。拟议的未来方向可能包括使用干细胞作为输送靶向神经胶质瘤干细胞的药物的载体,这与高级别神经胶质瘤对治疗的耐药性有关。总体而言,干细胞为基于细胞的治疗高级神经胶质瘤的方法提供了前所未有的机会,这种神经胶质瘤的预后持续不佳,并要求继续寻求治疗方法。

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