Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation
J. W. Ivey,
E. M. Wasson,
N. Alinezhadbalalami,
A. Kanitkar,
W. Debinski,
Z. Sheng,
R. V. Davalos,
S. S. Verbridge
Affiliations
J. W. Ivey
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA
E. M. Wasson
Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA
N. Alinezhadbalalami
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA
A. Kanitkar
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA
W. Debinski
Brain Tumor Center of Excellence, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
Z. Sheng
Virginia Tech Carilion Research Institute, Roanoke, VA 24061, USA; Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA; Faculty of Health Science, Virginia Tech, Blacksburg, VA 24061, USA
R. V. Davalos
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA; Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA; Brain Tumor Center of Excellence, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA; Faculty of Health Science, Virginia Tech, Blacksburg, VA 24061, USA
S. S. Verbridge
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA; Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA; Brain Tumor Center of Excellence, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA; Faculty of Health Science, Virginia Tech, Blacksburg, VA 24061, USA
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.
