Hearing loss, the most common form of human sensory deficit, is the partial or total inability to hear sound in one or both ears. It may be a sudden or a progressive impairment that gradually gets worse over time. Depending on the cause, it can be mild or severe, temporary or permanent. It may be a bilateral loss occurring in both ears or unilateral. Hearing loss may be fluctuating, that is, varying over improving at times and getting worse at other times. In other cases, hearing loss is stable, not changing at all with time. Hearing loss is caused by many factors, including genetics, age, exposure to noise, illness, chemicals, and physical trauma. Hearing loss may affect all ages, delaying speech and learning in children, and causing social and vocational problems for adults. 1
Hearing dysfunctions can be classified by type, degree, configuration, time of onset, etiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and neuro sensory hearing loss 2. Conductive hearing loss results from interference with the mechanical transmission of sound through the external and middle ear; it can be congenital, as a consequence of anatomic abnormalities, but it can commonly be acquired following middle ear inflammatory pathologies. Neuro sensory hearing loss results from failure to transduce vibrations to neural impulses in the cochlea and usually is a consequence of an irreversible damage to the differentiated cells which make up the organ of hearing and the acoustic paths at various levels. 3 Mixed hearing loss involves a combination of these two types in the same ear 1
Clearly in the etiology of the neuro sensory hearing loss are relevant many chemical toxic factors, like many pharmacological substances or physic agents like noise which induce degenerative or apoptotic damages, which however manifest themselves in a monotonous way with the loss not only of the cytological structure but also of the dedicated function: in this case the acoustic ability. In the binomial structure-function, as it is reasonable to expect a neuro sensory hearing loss in the case of lesion, it is equally reasonable to expect that an auditory recovery demonstrated with a tonal audiometric examination is supported by cellular regeneration. Such correspondence is considered specific both in Legal and Occupational Medicine, where there are tables dedicated to the interpretation of the indemnity.
In the present work we record an observational study on neuro sensory hearing loss using stem cell growth and differentiation factors (SCDSFs) which have demonstrated that these factors collected at the early developmental stages of Zebrafish embryo – just at the beginning of stem cell differentiation – are able to regenerate human adipose-derived stem cells (hASCs) 4¹.
These researches demonstrated that SCDSFs are significant in activating important genes, which counteract human cells senescence. Indeed, these factors represent very effective tools to increase stem cell expression of multipotency, reducing the expression of the beta-galactosidase marker and enhancing the stemness genes Oct-4, Sox-2 and c-Myc.5
Furthermore, it was possible to activate the gene expression of TERT, the catalytic subunit of telomerase, and the transcription of Bmi-1, 6, 7 which plays a role in counteracting senescence, as a key repressor of telomerase-independent aging. 8, 9.
Based on researches on stem cell rejuvenation and differentiation, we have also conducted studies on the prevention of cell degeneration and tissue regeneration without stem cell transplantation.10 Studies in this field have shown that the prevention of cell degeneration is only possible if all the factors taken at the different stages of stem cells’ multiplication and differentiation are administered together. We have demonstrated this in a recent study on the ability of SCDSFs to prevent neurodegeneration in hippocampal cells of the CA1 zone in mice 11. This experiment demonstrates that the degeneration of the cells of a tissue can be avoided only by administrating all the differentiating factors able to regenerate and differentiate the stem cells of that tissue, that is to say when the information is complete and redundant. This study confirms previous findings demonstrating that early development of zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues 7. These findings have open a promising way for the approaches promoting the rejuvenation and regeneration of different tissues, by-passing stem cell transplantation.
In the present clinical trial we have used SCDSFs to study the possible reversion of neurosensory hearing loss, until now considered an irreversible condition.