A UPV/EHU study published in the prestigious journal Stem Cell Research & Therapy has proven that stem cells extracted from human dental pulp can be transformed into excitable neuronal cells and has highlighted the potential of these easily accessible cells for nerve tissue engineering. This finding will enable the furthering of advances in cell therapy for treating various neurodegenerative diseases, such as Huntington's disease and epilepsy.

“An adult neuron cannot be divided. When you lose it, you lose it for ever. And unlike other organs, the brain has a comparatively low capacity for natural regeneration due to its low presence of stem cells,” said Gaskon Ibarretxe, a researcher in the UPV/EHU’s Signaling Lab research group. The scientific community is looking for a way to obtain functional neurons that can be transplanted to restore impairments in neurodegenerative pathologies, brain lesions, strokes, etc. “But if the cells transplanted into the brain are to be able to integrate into a damaged brain circuit and replace the lost neurons, they need to be able to produce electrical impulses,” added the researcher José Ramón Pineda, co-author of the study and a researcher in the group.

Stem cells have the capacity to divide and differentiate into different types of specialised cells. The UPV/EHU research group has obtained cells very similar to neurons; they “manage to produce electrical impulses like those of neurons by means of the differentiation of stem cells in human dental pulp, the soft tissue located inside the tooth,” they said. The main milestone of this study was “the obtaining of cells that display functional excitability and which synthesise a type of neurotransmitter that regulates neuronal activity, without having been genetically modified; the primary dental cells were simply cultured with differentiation factors and were subjected to precise stimuli to generate cells with neuronal electrophysiological activity”, said the researchers of the Signaling Lab at the UPV/EHU. This had never been achieved before.”

Resembling inhibitory neurons

Neurotransmitters are substances released by neurons that can send excitatory or inhibitory signals to make neurons generate an electrical impulse or not. “The cells that we managed to differentiate are capable of synthesising a neurotransmitter known as GABA,” explained the researchers. “It is a type of inhibitory signalling, in other words, it controls whether the neuron that receives it fires electrical impulses or not. And that is very important because there are neurodegenerative diseases such as Huntington's disease or conditions such as epilepsy in which there is a selective death of those types of cells in specific areas of the brain, and a resulting hyper-excitability of the brain circuitry”.

Ibarretxe and Pineda, lecturers in the UPV/EHU’s Department of Cell Biology and Histology, expressed great optimism when referring to the new avenues that can be explored on the basis of this finding: “We believe that these cells could be integrated into a damaged brain circuit and replace lost neurons, and thus reconnect with existing neurons and eventually regenerate the entire lost area functionally. This finding suggests a different approach to traditional cell therapy applied to the nervous system, which until now has been based, above all, on reducing inflammation, on neuroprotecting what remained alive, but not on replacing what has been lost. This opens a new door to the future of personalised medicine.”

That is in fact the next step in this research: “to transplant these cells into living animals and see if they are integrated into the brain circuit and reconnect with the host's neurons. We obtained cells that generate electrical impulses characteristic of neurons that are not yet fully mature, but we are aware that they must generate trains of electrical impulses and be correctly integrated into a neuronal circuit. We haven’t achieved that yet”. The UPV/EHU researchers admitted that “there is a long road ahead, but we know it’s going to be very promising. We believe that these cells have a great chance of being implemented in the clinical setting. The fact that they are transplanted at a relatively immature stage could even encourage their plasticity and integration into already developed brain circuits”. The researchers added that these cells in fact offer an inherent advantage: “They are cells that do not have a tendency to generate tumours; on the contrary, it has been proven that they are very stable cells and differentiate better than other types of human stem cells into neurons,” they concluded.

Additional information

This study comes within the framework of the PhD thesis by Beatriz Pardo-Rodríguez, co-supervised by the researchers José Ramón Pineda-Martí and Gaskon Ibarretxe in the Department of Cell Biology and Histology. Researchers from the Achucarro Basque Centre for Neuroscience have also collaborated in the study.

Pineda and Ibarretxe lecture at the UPV/EHU on the degree courses in Medicine and Biomedical Engineering and on the Master’s course in Biomedical Research.

Bibliographic reference

B. Pardo-Rodríguez, A. M. Baraibar, I. Manero-Roig, J. Luzuriaga, J. Salvador-Moya, Y. Polo, R. Basanta-Torres, F. Unda, S. Mato, Gaskon Ibarretxe† and Jose Ramon Pineda

Functional differentiation of human dental pulp stem cells into neuron-like cells exhibiting electrophysiological activity

Stem Cell Research & Therapy

DOI: 10.1186/s13287-025-04134-7