用于按需对胶质母细胞瘤进行便捷活检的神经管导管

Martha I Betancur, Ayden Case, Ekaterina Ilich, Nalini Mehta, Sean Meehan, Sabrina Pogrebivsky, S. T. Kier, Kevin Stevenson, Barun Brahma, Simon Gregory, Wei Chen, David M Ashley, Ravi Bellamkonda, Nassir Mokarram
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摘要

有效治疗胶质母细胞瘤(GBM)患者的一大障碍是缺乏有关肿瘤进展、演变和治疗反应的纵向信息。 在本研究中,我们报告了在两种啮齿类动物模型中使用神经束启发的导管(即对齐纳米纤维装置)来实现按需进入 GBM 肿瘤。根据实验的需要,我们选择了人源化 U87MG 异种移植肿瘤和/或 F98-GFP+ 合成大鼠肿瘤模型,以测试该装置在对肿瘤及其微环境进行连续取样时的安全性和功能性。 排列整齐的纳米纤维装置安全可靠,能提供大量优质基因组材料,适用于omics分析,并能产生足够数量的活细胞用于体外扩增和筛选。转录组和基因组分析表明,从该装置提取的材料与皮质内原发性肿瘤(体内模型)的材料具有连续性。 这些结果证明了这种受神经束启发、排列整齐的纳米纤维装置的潜力,它是一种按需、安全、微创的接入点,可对肿瘤及其微环境进行快速、高通量、纵向评估,从而制定出更明智的临床治疗策略。
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A Neural Tract-Inspired Conduit for Facile, On-Demand Biopsy of Glioblastoma
A major hurdle to effectively treating glioblastoma (GBM) patients is the lack of longitudinal information about tumor progression, evolution, and treatment response. In this study, we report the use of a neural tract-inspired conduit containing aligned polymeric nanofibers (i.e., an aligned nanofiber device) to enable on-demand access to GBM tumors in two rodent models. Depending on the experiment, a humanized U87MG xenograft tumor and/or F98-GFP+ syngeneic rat tumor models were chosen to test the safety and functionality of the device in providing continuous sampling access to the tumor and its microenvironment. The aligned nanofiber device was safe and provided a high quantity of quality genomic materials suitable for omics analyses and yielded a sufficient number of live cells for in vitro expansion and screening. Transcriptomic and genomic analyses demonstrated continuity between material extracted from the device and that of the primary, intracortical tumor (in the in vivo model). The results establish the potential of this neural tract-inspired, aligned nanofiber device as an on-demand, safe, and minimally invasive access point which enables rapid, high-throughput, longitudinal assessment of tumor and its microenvironment, leading to more informed clinical treatment strategies.
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