Building inner ear organoids from human pluripotent stem cells through directed self-assembly

  • Assistant Professor, Indiana University School of Medicine
      Karl Koehler, PhD is an Assistant Professor of Otolaryngology-Head and Neck Surgery at Indiana University School of Medicine. He joined the faculty after completing his PhD degree in Medical Neuroscience in 2014 under the mentorship of Dr. Eri Hashino. Dr. Koehler began his career studying how embryonic and induced pluripotent stem cells could be used to produce neurons to treat hearing loss patients. His early work, published in Nature and Nature Protocols, detailed a novel culture system for growing mini inner ear organs, known as inner ear organoids, from mouse pluripotent stem cells. He then spearheaded an effort to decode the signaling mechanisms required to coax human pluripotent stem cells to become inner ear organoids. This work was recently published in Nature Biotechnology in June 2017. His research now focuses on using the organoid culture system as a platform to develop regenerative therapies for the inner ear and various craniofacial tissues. His work is funded by grants from the National Institute of Health and the Indiana Clinical and Translational Research Institute.


    The human inner ear contains ~75,000 sensory hair cells that detect sound or movement via mechanosensitive hair bundles and transmit signals to the brain via specialized sensory neurons. Inner ear sensory cells derived from pluripotent stem cells would provide a valuable model for drug testing, yet a defined differentiation approach has been challenging to identify. Our group has established a step-wise method for generating inner ear organoids, with functioning hair cells, from human pluripotent stem cells. In a 3D culture system, we modulated TGF, BMP, FGF, and WNT signaling to direct the self-organization of multiple otic vesicle-like cysts from a homogenous cell aggregate. Over a 60-day period, the vesicles developed into multi-chambered organoids with sensory epithelia containing hair cells, reminiscent of the membranous organs of the inner ear. This presentation will discuss the process of making inner ear organoids as well as the potential applications of this technique as a powerful tool for investigating human inner ear development and drug discovery.

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