Ultrastructural evidence for hair cell regeneration in the mammalian inner ear

Abstract

It has long been thought that hair cell loss from the inner ears of mammals is irreversible. This report presents scanning electron micrographs and thin sections of the utricles from the inner ears of guinea pigs that show that, after hair cell loss caused by treatment with the aminoglycoside gentamicin, hair cells reappeared. Four weeks after the end of treatment, a large number of cells with immature hair bundles in multiple stages of development could be identified in the utricle. Thin sections showed that lost type 1 hair cells were replaced by cells with a morphology similar to that of type 2 hair cells. These results indicate an unexpected capacity for hair cell regeneration in vivo in the mature mammalian inner ear.

Atoh1, an Essential Transcription Factor in Neurogenesis and Intestinal and Inner Ear Development: Function, Regulation, and Context Dependency

“…In mammals, HCs of the vestibular system can regenerate and ectopic expression of Atoh1 in mature animals results in supernumerary HCs (Forge et al 1993;Lopez et al 1997;Wang et al 2010); however, Atoh1 has limited ability to generate ectopic HCs in the mature cochlea. Several groups have successfully generated ectopic HCs by transfecting cochlear explants or by in utero electroporation with Atoh1 under the control of a constitutively active promoter (Zheng and Gao 2000;Gubbels et al 2008).…”

Development of the zebrafish inner ear

“…In mammalian embryos, supporting cells in the cochlea can trans-differentiate into hair cells but typically do not renew cell populations by reentry into the cell division cycle . Moreover, little or no hair cell regeneration occurs within the mammalian cochlea postembryonically, although regeneration apparently does occur in the utricle (Forge et al, 1993; reviewed by Staecker and Van De Water, 1998). By understanding how hair cell regeneration is normally initiated in other sensory epithelia, it may be possible to stimulate this process in the mammalian cochlea.…”

Essential role of retinoblastoma protein in mammalian hair cell development and hearing

“…Other pathways, most notably the retinoic acid and Notch pathways, are involved in the induction of hair cells either from the progenitor cell pool or from the supporting cell pool at early stages of development (3)(4)(5). Hair cells of mammalian inner ears, unlike those in lower vertebrates, do not undergo spontaneous regeneration, even though vestibular supporting cells retain a limited capacity to divide (6,7). As a consequence, damage to hair cells often results in irreversible deficits in hearing and balance.…”