Replacement of hair cells after laser microbeam irradiation in cultured organs of corti from embryonic and neonatal mice

Abstract

This study examined the potential for hair cell regeneration in embryonic and neonatal mouse organs of Corti maintained in vitro. Small numbers of hair cells were killed by laser microbeam irradiation and the subsequent recovery processes were monitored by differential interference contrast (DIC) microscopy combined with continuous time-lapse video recordings. Replacement hair cells were observed to develop in lesion sites in embryonic cochleae and on rare occasions in neonatal cochleae. In embryonic cochleae, replacement hair cells did not arise through renewed proliferation, but instead developed from preexisting cells that changed from their normal developmental fates in response to the loss of adjacent hair cells. In cochleae established from neonates, lost hair cells usually were not replaced, but 11 apparently regenerated hair cells and a single hair cell labeled by 3H-thymidine were observed as rare responses to the creation of hair cell lesions in these organs. The results indicate that the organ of Corti can replace lost hair cells during embryonic and on rare occasions during early neonatal development. The ability of preexisting cells to change their developmental fates in response to hair cell death is consistent with the hypothesis that during embryonic development hair cells may inhibit neighboring cells from specializing as hair cells. In neonatal cultures, the rare occurrence of apparently regenerated hair cells indicates that some cells in the postembryonic organ of Corti retain response mechanisms that can lead to self-repair.

Auditory hair cell precursors immortalized from the mammalian inner ear

“…1993; Warchol et al 1993;Kelley et al 1995;Fekete 1996;Jones & Corwin 1996). During the ¢nal mitotic divisions, which occur in the mouse at E12^E14, pluripotent progenitors give rise to non-sensory precursors (NSP) and prosensory precursors (PSP).…”

“…A pluripotent progenitor passes through its last mitosis at approximately E14, giving rise to a non-sensory and a prosensory precursor. The prosensory precursor has the potential to di¡erentiate without undergoing mitosis (Kelley et al 1993(Kelley et al , 1995 into either a committed hair cell precursor or a committed supporting cell precursor. UB/OC-1 has been immortalized prior to the expression of Brn3.1.…”

“…The mammalian cochlea possesses just a few thousand sensory hair cells (Echteler et al 1994), for which there is no demonstrable regeneration after embryonic development (Kelley et al 1995;Corwin & Oberholtzer 1997;Zine & Ribaupierre 1998). Progressive hearing loss is common and most forms of deafness are irreversible.…”

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

“…These observations led to the general conclusion that the vestibular sensory epithelia and the auditory sensory epithelia have different regenerative capacities (Stone et al 1998). A possible explanation for this difference is that the differentiated cell types that contribute to the highly specialized architecture of the organ of Corti lose proliferative and regenerative capacity during postnatal maturation of the auditory system (Lim and Rueda 1992;Kelley et al 1995).…”

Genetic and pharmacological intervention for treatment/prevention of hearing loss

“…There is a brief period during mouse embryonic development when new hair cells can be induced through direct transdifferentiation to supplement or replace the initial population (Kelley et al, 1993;Kelley, Talreja, & Corwin, 1995). Moreover, there is good evidence that limited hair cell regeneration occurs in the mammalian vestibular system, even in humans (Forge, Li, Corwin, & Nevill, 1993;Warchol, Lambert, Goldstein, Forge, & Corwin, 1993).…”