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01 August 2008

Novel approaches to treating sensorineural hearing loss. Auditory genetics and necessary factors for stem cell transplant

Petros V. Vlastarakos, Thomas P. Nikolopoulos, Evangelia Tavoulari, Catherine Kiprouli, Eleftherios Ferekidis

Med Sci Monit 2008; 14(8): RA114-125 :: ID: 865804

Abstract

Sensorineural hearing loss is a chronic disease, with a serious impact on human communication and quality of life. Exposure to various factors can lead to irreversible hearing impairment, as the auditory epithelium in humans comprises terminally differentiated cells. By contrast, the inner ear of lower vertebrates and invertebrates shows regenerative capacity. Efforts to regenerate the damaged human inner ear may involve renewed cell proliferation, or transplanting cells that can differentiate into sensory cells. Literature review. Animal studies, in vitro studies, retrospective-cohort studies, community-based case-controls, clinical guidelines, and review articles. Embryonic stem cells, inner ear stem cells, and stem cells from other tissues (i.e., neural tissue, hematopoietic system) may be candidates for restoring the auditory epithelium. Transcriptional regulation of p27kip1 is the primary determinant of terminal mitosis and the final number of postmitotic progenitors of hair and supporting cells. Basic helix-loop-helix transcription factor Math1 was found to be necessary and sufficient for the production of auditory hair cells. Notch signaling seems to play a major role in the regulation of Math1, through lateral inhibition. Brn3c, Gfi1, and Barhl1 are also specific transcription factors that have been implicated in hair cell maintenance and consequent survival. Evidence concerning development, maintenance, and regeneration of hair cells is still at an embryonic stage. Combined data, as attempted in the present study, will lead to a more successful management of deafness.

Keywords: Hearing Loss, Sensorineural - therapy, Ear, Inner - pathology, Stem Cell Transplantation - methods, Auditory Pathways - metabolism, Animals

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