Development of otic organoids and their current status

Abstract

The inner ear is responsible for both hearing and balance in the body, and since the initial development of otic (inner ear) organoids from mouse pluripotent stem cells (PSCs) in 2013, significant advances have been made in this field. Bone morphogenetic proteins, fibroblast growth factors, and Wnt agonists, which are signaling molecules in the early development of the inner ear, can induce PSCs into the otic fate. In the inner ear, hair cells and the surrounding supporting cells are essential for proper function and structure. Recent advancements in otic organoid research have enabled the generation of cells that closely resemble these key components. The developed otic organoids contain both hair cell-like cells and supporting cells, which have been confirmed to have the intrinsic function of those cell types. Otic organoids have been used for disease modeling and are expected to be more widely applied in various areas of research on the inner ear. However, the otic organoids developed to date remain immature. Although they mimic hair cells, their properties resemble vestibular (balance) hair cells more closely than cochlear (auditory) hair cells. The ultimate goal of research on the inner ear is hearing restoration and prevention; thus, it is essential to produce otic organoids that contain cochlear hair cells. In addition, the organ of Corti—a cell arrangement unique to the cochlea—has not yet been simulated. Along with a description of the current status of otic organoids, this review article will discuss future directions for otic organoids in inner ear research.