Thyroid hormone augmentation accelerates hair cell maturation in human cochlear organoids

Human pluripotent stem cell-derived cochlear organoids are promising tools for studying human cochlear development and disease. However, the maturation of hair cells in these organoids is slow, requiring 200 days to express the mature outer hair cell marker Prestin. To promote hair cell maturation, we tested the effects of the thyroid hormone thyroxine on Prestin expression in human cochlear organoids. Thyroxine supplementation significantly increases the number of Prestin-positive hair cells in an age-dependent manner. Additionally, transcriptomic analyses reveal the upregulation of mature outer hair cell genes and the downregulation of immature hair cell genes in thyroxine-treated hair cells. Furthermore, thyroxine-treated hair cells exhibit electromotility, a hallmark of functional outer hair cells. These results identify thyroid hormones as a means to accelerate the maturation of outer hair cells in human cochlear organoids, thereby establishing an improved human in vitro model for pre-clinical investigation of sensorineural hearing loss.