Inner ear organoids: progress and outlook, with a focus on the vascularization

Abstract

The inner ear is a complex organ that encodes sound, motion and orientation in space. Given the complexity of the inner ear, it is not surprising that treatments are relatively limited despite the fact that, in 2015, hearing loss was the fourth leading cause of years lived with disability (YLDs) worldwide. Inner ear organoid models are a promising tool to advance the study of multiple aspects of the inner ear to aid the development of new treatments and validate drug-based therapies. The blood supply of the inner ear plays a pivotal role in growth, maturation, and survival of inner ear tissues and their physiological functions. This vasculature cannot be ignored in order to achieve a truly in vivolike model that mimics the microenvironment and niches of organ development. However, this aspect of organoid development has remained largely absent in the generation of inner ear organoids. The current review focuses on three-dimensional (3D) inner ear organoid and how recent technical progress in generating in vitro vasculature can enhance the next generation of these models.

Construction of organ of Corti organoid to study the effects of berberine sulfate on damaged auditory cells

“…The anatomical location of the auditory organ of the inner ear is deeply buried in the temporal side of the head, which makes it impossible to pursue the conventional treatment through surgical treatment, drug delivery, and tissue engineering technology 43,44 . Recently, kinds of organoid models are promising tools to advance the study of regenerative medicine, which validates the rapid development of new treatments of drug or gene‐based therapies 20 . Up to now, the overwhelming majority of inner ear organoids derived from the stem cells, especially PSCs 45 .…”

“…43,44 Recently, kinds of organoid models are promising tools to advance the study of regenerative medicine, which validates the rapid development of new treatments of drug or gene-based therapies. 20 Up to now, the overwhelming majority of inner ear organoids derived from the stem cells, especially PSCs. 45 However, these stem cell-based organoids unable to structurally and functionally mimic the organ of Corti microenvironment in vivo.…”

“…Otic organoids derived from hiPSCs, which recapitulate many facets of human development and native cellular diversity, are being widely used for disease modeling and preliminary testing of biological and chemical‐based therapeutics for human inner ear dysfunction 19 . However, previous stem cell‐based organoids are far from mimicking the structure and function of the intrinsic organ of Corti 20 . 3D scaffolds have many advantages in constructing organoids, 21–23 but construction of inner ear organoids using 3D scaffolds has not been reported.…”

“…19 However, previous stem cell-based organoids are far from mimicking the structure and function of the intrinsic organ of Corti. 20 3D scaffolds have many advantages in constructing organoids, [21][22][23] but construction of inner ear organoids using 3D scaffolds has not been reported.…”

Graphene Hybrid Inner Ear Organoid with Enhanced Maturity

“…Despite several research trials on the development of the inner ear, cellular models of the inner ear have not gained popularity as drug discovery platforms. Over the past decade, studies have focused on optimizing and improving the development of inner ear organoids (IEOs). − These studies have demonstrated that embryonic-stem-cell (ESC)- and induced pluripotent stem-cell-based IEOs can possess sensory hair cells, supporting cells, and neurons based on the definitive ectoderm in embryonic development. − …”