In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss?

Abstract

The sensory cells of the inner ear, called hair cells, do not regenerate spontaneously and therefore, hair cell loss and subsequent hearing loss are permanent in humans. Conversely, functional hair cell regeneration can be observed in non-mammalian vertebrate species like birds and fish. Also, during postnatal development in mice, limited regenerative capacity and the potential to isolate stem cells were reported. Together, these findings spurred the interest of current research aiming to investigate the endogenous regenerative potential in mammals. In this review, we summarize current in vitro based approaches and briefly introduce different in vivo model organisms utilized to study hair cell regeneration. Furthermore, we present an overview of the findings that were made synergistically using both, the in vitro and in vivo based tools.

Keywords: Cell lines; Hair cell regeneration; Model organisms; Organoids; Stem cells.

Figure 1.. Approaches and Model Organisms in Regenerative Research of the Inner Ear.

Cell lines, 3D-organoids, and explants are in vitro approaches used to perform drug screening, disease modeling, and to explore stem cell therapies. In vivo model organisms like fish, chicken, and the mouse are used to study development and endogenous regeneration to develop new hypotheses and validate findings from in vitro based experiments.

Figure 2.. Mechanisms of Hair Cell Regeneration.

HCs regenerate through a) transdifferentiation, where a SC directly converts into a HC or b) through mitotic regeneration, where SCs first proliferate, then the daughter cells differentiate into new HCs and/or SCs. Different molecular pathways involved were identified.