Integration of neural cells derived from human dental pulp stem cells into the brain synaptic network

• Autores: Beatriz Pardo Rodríguez
• Directores de la Tesis: José Ramón Pineda Martí (dir. tes.), Gaskon Ibarretxe Bilbao (codir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2025
• Idioma: inglés
• Programa de doctorado: Programa de Doctorado en Investigación Biomédica por la Universidad del País Vasco/Euskal Herriko Unibertsitatea
• Menciones:
  • Internacional
• Calificación: Sobresaliente Cum Laude
• Materias:
  • Ciencias médicas
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • The lack of effective treatment options combined with the rising incidence and prevalence of neurodegenerative diseases has brought attention into stem cell based neuroregenerative therapies, which may be able to repair damaged neural tissue through paracrine effects or cell replacement. In this context, human dental pulp stem cells (hDPSCs) constitute a promising alternative due to their unique features including their neural crest origin, their ease of extraction, their ability to release neuroprotective factors and their expression of mature neuronal and glial markers. However, a better understanding of their real capacity to give rise to functional neurons is still needed.

    During this doctoral thesis, we have studied hDPSCs capacity to differentiate into functional neurons that can integrate within the synaptic network of the adult murine brain. For that, we optimised existing hDPSC neurodifferentiation protocols and characterized the reversibility of fetal serum-induced changes when cells were switched from serum containing to serum-free media. Furthermore, we strengthened hDPSC differentiation into functional neurons with retinoic acid (RA) and pulses of potassium chloride (KCI). In addition, we assessed hDPSCs synaptic integration in vivo by grafting the cells into the hippocampus of C57BL/6J non-immunosuppressed mice.