Electrical Stimulation of Neuroblastoma Cells: Effects on Differentiation

• Autores: Daniel Martín Fernández
• Directores de la Tesis: Paula Daza Navarro (dir. tes.)
• Lectura: En la Universidad de Sevilla ( España ) en 2026
• Idioma: inglés
• Número de páginas: 171
• Enlaces
  • Tesis en acceso abierto en: Idus
• Resumen

  • This work focuses on the use of electrical stimulation to promote the neuronal differentiation of neuroblastoma cells in vitro.

    Neuroblastoma is a pediatric cancer in which the degree of maturation of the cells strongly influences its outcome. This thesis investigates whether electrical stimulation can promote a more differentiated, neuron-like state in cultured neuroblastoma cells.

    A custom system was built to deliver well?defined electrical signals to cells. The system allows for complete control over the waveform, amplitude and frequency of the ES signal delivered. The system uses a commercial electrode setup that was characterized electrochemically through standard procedures.

    A wide range of ES signals were tested and the optimal protocol for neuroblastoma cell differentiation was defined. Low amplitude stimulation modestly favored continued growth and high fields at low frequencies caused damage. A biphasic square signal at a 500mV-100Hz yielded the most reliable gains in differentiated morphology. The optimal protocol was expressed by its fundamental electrical parameters independent of the setup. The effects of electrical stimulation on neuroblastoma cells were measured by optical, fluorescence and electron microscopy staining of structural and fate markers and with complementary assays of proliferation, DNA damage, and tumorspheres. All of these assays demonstrated the effectiveness of ES promoting the onset of differentiation.

    Analyses of gene expression and protein signaling carried out suggested engagement of pathways commonly linked to neuronal maturation and transcription factors that support differentiation. Additional experiments indicated that the effects of electrical stimulation are transmitted to the surrounding environment through paracrine signaling, mediated by interleukin-6. The mechanisms of electrically induced neuronal differentiation were also linked to autophagy.

    Together, these findings demonstrate that electrical stimulation can induce differentiation of neuroblastoma cells in vitro, thereby reducing their proliferative capacity and suggesting its potential as a complementary therapeutic approach.