Progenitor Cells from the Adult Human Inner Ear

Abstract

Loss of inner ear hair cells leads to incurable balance and hearing disorders because these sensory cells do not effectively regenerate in humans. A potential starting point for therapy would be the stimulation of quiescent progenitor cells within the damaged inner ear. Inner ear progenitor/stem cells, which have been described in rodent inner ears, would be principal candidates for such an approach. Despite the identification of progenitor cell populations in the human fetal cochlea and in the adult human spiral ganglion, no proliferative cell populations with the capacity to generate hair cells have been reported in vestibular and cochlear tissues of adult humans. The present study aimed at filling this gap by isolating colony‐forming progenitor cells from surgery‐ and autopsy‐derived adult human temporal bones in order to generate inner ear cell types in vitro. Sphere‐forming and mitogen‐responding progenitor cells were isolated from vestibular and cochlear tissues. Clonal spheres grown from adult human utricle and cochlear duct were propagated for a limited number of generations. When differentiated in absence of mitogens, the utricle‐derived spheres robustly gave rise to hair cell‐like cells, as well as to cells expressing supporting cell‐, neuron‐, and glial markers, indicating that the adult human utricle harbors multipotent progenitor cells. Spheres derived from the adult human cochlear duct did not give rise to hair cell‐like or neuronal cell types, which is an indication that human cochlear cells have limited proliferative potential but lack the ability to differentiate into major inner ear cell types. Anat Rec, 303:461–470, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies

“…The ability to be propagated as spheres or to generate HCs declines with age, and is largely lost by P30 [ 91 , 92 ]. This matches results from tissues obtained from adult human cochlea, where only a single sphere was cultured from ten individual samples [ 93 ].…”

“…Without sufficient numbers of supporting cells, long-term functionality is very likely compromised [ 130 ]. Sphere-forming capability from the adult human cochleae is quite poor when compared to adult human utricles, indicating a more stringent regulation of proliferation [ 93 ]. Recently, supporting cell and IHC proliferation were both demonstrated after the transduction of the oncogene MYC in conjunction with increased NOTCH signaling in adult cochlear cells [ 131 ].…”

Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons

“…Yet, it is difficult to understand why auditory neuroprogenitors from the A/J mouse strain exhibit such high self-renewal ability compared to previously described models. In mice, proliferation of SGN progenitors is typically observed during the first postnatal week, but rapidly decreases with age to virtually no regeneration in adults (Oshima et al, 2007;Moon et al, 2018;Senn et al, 2020). The failure of the adult inner ear to regenerate following injury might be explained by the low intrinsic self-renewal ability of mammalian auditory neuroprogenitors.…”

Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells

“…Activation of quiescent progenitor cells residing in the sensory epithelium of the inner ear or replacing missing hair cells with new hair cells derived from pluripotent stem cells (PSCs) could be a potential cure. Despite the identification of multipotent cell populations in the human fetal cochlea and in the adult human spiral ganglion, no proliferative cell populations with the capacity to give rise to hair cells have been reported in adult humans ( Senn et al., 2020 ).…”