Thyroid hormone augmentation accelerates hair cell maturation in human cochlear organoids

Area of Science:

• Regenerative Medicine
• Developmental Biology
• Otolaryngology

Background:

• Human pluripotent stem cell-derived cochlear organoids model human inner ear development and disease.
• Hair cell maturation in these organoids is slow, taking 200 days for mature outer hair cell marker Prestin expression.

Purpose of the Study:

• To investigate the effect of thyroid hormone thyroxine on accelerating hair cell maturation in human cochlear organoids.
• To establish an improved in vitro model for pre-clinical research on sensorineural hearing loss.

Main Methods:

• Supplementation of human cochlear organoids with thyroxine.
• Assessment of Prestin expression as a marker for outer hair cell maturation.
• Transcriptomic analysis to evaluate gene expression changes.
• Electromotility assays to determine hair cell functionality.

Main Results:

• Thyroxine significantly increased the number of Prestin-positive hair cells in an age-dependent manner.
• Transcriptomic analysis showed upregulation of mature outer hair cell genes and downregulation of immature hair cell genes.
• Thyroxine-treated hair cells demonstrated electromotility, indicating functional maturation.

Conclusions:

• Thyroid hormone thyroxine effectively accelerates outer hair cell maturation in human cochlear organoids.
• This finding provides an enhanced in vitro model for studying sensorineural hearing loss.
• The study highlights thyroid hormones as a key factor in promoting hair cell development for therapeutic research.