Brazilian study received the Young Scientist prize at the World Otorhinolaryngology Congress in South Korea

Stem cells could help regenerate facial nerves
2013-08-14

Brazilian study received the Young Scientist prize at the World Otorhinolaryngology Congress in South Korea.

Stem cells could help regenerate facial nerves

Brazilian study received the Young Scientist prize at the World Otorhinolaryngology Congress in South Korea.

2013-08-14

Brazilian study received the Young Scientist prize at the World Otorhinolaryngology Congress in South Korea

 

By José Tadeu Arantes

Agência FAPESP – “The expression of feelings on one’s face is one of the most unique human abilities, making the loss of the movements of this musculature very distressing.” With these words, medical doctor Raquel Salomone summed up her motivation for her study on the regeneration of facial nerves using stem cells, with which she obtained her doctorate in 2012.

Sent to the International Federation of Otorhinolaryngological Societies World Congress in Seoul, South Korea, the study received the Young Scientist prize, which was awarded during the event.

The study “Evaluation of the regeneration of the facial nerve in rats after implantation of differentiated bone marrow stem cells in vitro” was undertaken through a FAPESP fellowship and with the mentorship of Ricardo Ferreira Bento, full professor at the Department of Ophthalmology and Otorhinolaryngology at Universidade de São Paulo’s Medical School (FM-USP).

The proposal was to seek a solution for a lesion on the seventh nerve of the cranium caused by trauma or viral infection and resulting in paralysis and subsequent asymmetry of the face.

“This causes severe hardship for the affected person, such as the inability to blink, which can cause ulcers of the cornea and blindness; the impossibility of controlling salivary glands and eating; the loss of sensitivity of the auricular pavilion and the external ear; and aesthetic deformity, with all its psychological impact,” said Salomone.

The surgical reconstruction of the nerve has limited results. Residual paralysis, hypotonia (reduction of the muscle tone) and synkinesis (the association of involuntary movements with voluntary movements) are some of the side effects.

“What most compelled me and sincerely still keeps me awake at night was the realization that even at the hands of the best surgeons, the results are so unsatisfactory. Why do some of the patients evolve well and others not? Why do the existing treatments work for some and others not? I would like to be able to do something to help. That was what drove my study,” comments Salomone, who is a supervisor at the Peripheral Facial Paralysis Clinic and an otorhinolaryngologist at FM-USP’s Hospital da Clinicas.

Scientists have known for some time that axons, which constitute nerves, are coated by a cover formed by Schwann cells, which provide the nerve all the support it needs, such as growth factors, among other things. Nerve regeneration therefore depends critically on this cell structure. The problem is that Schwann cells are scarce in an organism. To coat damaged cells, discovering a source would be necessary.

“We thought about utilizing stem cells to bridge this gap. As you know, stem cells can come from any type of cell, when duly stimulated. Therefore, our study was to investigate how stem cells, playing the role of Schwann cells, could favor the regeneration of the damaged nerve,” said Salomone.

The study was conducted in animals (rats) subjected to neurotmesis. This procedure consists of cutting a piece of the nerve and leaving a space between the two remaining parts. It is the worst type of lesion that can occur, much more serious than the majority of clinical cases. The idea was that if the stem cells were efficient in this extreme scenario, they would be even more effective in common lesions.

The animals were split into four groups. In the first, the two remaining parts of the selected nerve were connected by a hollow silicon tube; in the second, the tube was filled with an acellular gel; in the third, it was filled with undifferentiated stem cells; and finally, in the fourth, in was filled with Schwann-like differentiated stem cells.

“We found that all animals that received stem cells (undifferentiated or differentiated) had a much more significant improvement than those that received an empty tube or a tube filled with gel. We confirmed, therefore, our hypothesis that stem cells can really contribute to regeneration of the nerve,” said Salomone.

However, the experiment brought one surprise: undifferentiated stem cells had a better performance than differentiated cells. “The conclusion we reached was that this was due to the presence of the silicone tube. Because they are capable of performing multiple functions, the Schwann cells require more substrate to live – which was difficult because of the tube. The undifferentiated cells proved more capable of survival and acting in adverse conditions,” said Salomone.

The article resulting from the dissertation was published in Muscle & Nerve. The complete reference and abstract can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/23824709.

New projects

A São Paulo native who a obtained a medical degree from Universidade do Vale do Sapucaí in Pouso Alegre, Minas Gerais, Salomone joined the Otological and Lateral Cranial Surgery Specialization Program at FM-USP Hospital das Clinicas (HC) after finishing her medical residency.

“The HC also has a clinic specializing in peripheral facial paralysis, created by Ricardo Ferreira Bento, that serves approximately 40 patients per week. It is the largest number people served [in this medical specialization area] in Latin America and one of the largest in the world. I have directly experienced how devastating facial paralysis can be in the life of a human,” she said.

Salomone’s next step, the topic of her post-doctoral research, is implanting human stem cells subjected to neurotmesis. If the results are as good as expected, the following step will be a clinical trial involving adoption of the procedure in patients undergoing surgery to reconstitute the nerve.

 

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