Could regenerative techniques restore hearing or balance by replacing lost sensory cells in the inner ear? Lab-created inner-ear organs, described today in Nature Communications, could provide helpful three-dimensional models for testing potential therapies.
The lab-built sac-like structure above, about 1 millimeter in size, contains fully-formed balance organs resembling the utricle and saccule, which sense head orientation and movement and send impulses to the brain. The tiny organs were built from mouse embryonic stem cells in a 3-D tissue culture in work led by Jeffrey Holt, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and Eri Hashino, PhD, of the University of Indiana.
The organs were fully differentiated — complete with functioning sensory hair cells, supporting cells and neurons. As the cells grew up in the dish, they went through the developmental stages one would see in a real mouse embryo. Once mature, the sensory hair cells made specific proteins that one would expect in “native” inner-ear hair cells, including Myosin 7a (red) and Sox2 (green):
And in tests, the cells behaved like in real life: their tiny hairs responded to mechanical stimuli (head movement and gravity) by producing tiny but measurable electrical currents.
Holt, who has also restored hearing in deaf mice with gene therapy, hopes to use the lab-grown vestibular organs to develop biological therapies for balance problems in children, like those who visit Boston Children’s Balance and Vestibular Program each year.
“In addition to growing functional inner-ear organs, we can use this as a test system to develop new treatments for inner ear dysfunction,” he says. “For example, we could take advantage of genome editing with CRISPR/Cas9 to evaluate the role of genes and proteins involved in hair-cell development and function. These ‘organoids’ could also become a source for replacing lost or damaged hair cells — or perhaps even entire sensory organs for patients with vestibular dysfunction.”