Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation
Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation
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DOI：
10.34133/2019/8081315
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发表时间：
2019-01-01
期刊：
影响因子：
11
通讯作者：
Verbridge, S. S.
中科院分区：
文献类型：
--
作者：
Ivey, J. W.;Wasson, E. M.;Verbridge, S. S.
高频不可逆电穿孔（H-FIRE）是一种使用脉冲电场的技术，已被证明可以消融恶性细胞。为了评估H-FIRE治疗胶质母细胞瘤（GBM）（一种原发性脑肿瘤）的临床潜力，我们研究了高频波形对治疗抗性胶质瘤干细胞样细胞（GSC）群体的影响。我们证明，患者来源的GSC比原代正常星形胶质细胞更容易受到H-FIRE损伤。这种选择性为一定程度的恶性细胞靶向提供了机会，因为看到大量肿瘤细胞和肿瘤干细胞表现出类似的致死电场阈值，显著低于健康星形胶质细胞的致死电场阈值。然而，神经干细胞（NSC）群体也表现出类似的敏感性，这些脉冲。这一观察结果可能表明，在年轻患者与老年患者中应用这些疗法时应考虑不同的因素，其中保护NSC群体的重要性可能会对使用施加不同的限制。我们还证明了研究的三种患者来源的GSC系之间阈值的变异性，这表明在潜在的临床程序的开发中需要个性化的细胞特异性表征。未来的工作可能会提供关于观察到的这种患者依赖性变化的进一步有用的见解，这些变化可以为靶向和个性化治疗提供信息。
High-frequency irreversible electroporation (H-FIRE) is a technique that uses pulsed electric fields that have been shown to ablate malignant cells. In order to evaluate the clinical potential of H-FIRE to treat glioblastoma (GBM), a primary brain tumor, we have studied the effects of high-frequency waveforms on therapy-resistant glioma stem-like cell (GSC) populations. We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes. This selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric field thresholds, significantly lower than that of healthy astrocytes. However, neural stem cell (NSC) populations also exhibit a similar sensitivity to these pulses. This observation may suggest that different considerations be taken when applying these therapies in younger versus older patients, where the importance of preserving NSC populations may impose different restrictions on use. We also demonstrate variability in threshold among the three patient-derived GSC lines studied, suggesting the need for personalized cell-specific characterization in the development of potential clinical procedures. Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.