Stem Cell Differentiation Stage Factors (SCDSFs) Taken from Zebrafish Embryo During Organogenesis and Their Role as Epigenetics Regulators Able to Reverse Neurosensory Hearing Loss

P. Biava, Stefano Ciaurelli, Riccardo Benzi Cibelli, Gianpaolo Pisano
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Abstract

Hearing dysfunctions can be classified by type, degree, configuration, time of onset, aetiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and sensorineural. Conductive hearing loss (CHL) 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. Sensorineural hearing loss (SNHL) results from failure to transduce vibrations to neural impulses in the cochlean and 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. Mixed hearing loss involves a combination of these two types in the same ear. Studies in neuroscience 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. This study confirms previous findings demonstrating that early developmental zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues. 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.
从斑马鱼胚胎器官发生过程中提取的干细胞分化阶段因子(scdsf)及其作为表观遗传学调控因子逆转神经感觉性听力损失的作用
听力障碍可按类型、程度、形态、发病时间、病因以及对语言发育的影响进行分类。它们可分为传导性、混合性、中枢型和感音神经性。传导性听力损失(CHL)是由于声音通过外耳和中耳的机械传输受到干扰造成的;它可以是先天性的,作为解剖异常的结果,但它通常可以在中耳炎症病理后获得。感音神经性听力损失(SNHL)是由于耳蜗无法将振动传导到神经脉冲而引起的,是构成听觉器官和不同水平声通路的分化细胞受到不可逆损伤的结果。混合性听力损失包括这两种类型在同一只耳朵中的组合。神经科学领域的研究表明,只有在干细胞增殖和分化的不同阶段采取的所有因素同时施用,才能预防细胞变性。我们已经在最近的一项研究中证明了scdsf预防小鼠海马CA1区细胞神经退行性变的能力。该研究证实了先前的研究结果,表明早期发育的斑马鱼胚胎提取物可以作为从许多成人组织分离的人间充质干细胞(hMSC)的衰老调节剂。这些发现为绕过干细胞移植促进不同组织的恢复和再生开辟了一条有希望的途径。在目前的临床试验中,我们使用SCDSFs来研究神经感觉性听力损失的可能逆转,直到现在才被认为是不可逆的情况。
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