Home-grown inner ear cells

Researchers have developed a technique to grow "bona fide" hair cells of the inner ear from chick sensory tissue, reports a study in this week's PNAS. The approach could help hearing researchers understand how the inner ear of birds regenerates hair cells, the authors say.

"I think it's a remarkable study that beautifully illustrates the plasticity of progenitor cells from the avian inner ear," Jennifer Stone at the University of Washington told The Scientist.

Jeffrey Corwin at the University of Virginia and a postdoc in his lab, Zhengqing Hu, isolated supporting cells, known to produce hair cells in birds, fish, and amphibians, from the sensory epithelium of chicken embryos. The cultures produced spheres of sensory epithelia cells, including about 15 percent hair cells. The hair cells were complete with erect stereocilia, the sensory bundles that respond to stimuli.

"It really was quite a surprise to see those hair bundles sticking out," Corwin told The Scientist. Hearing researchers have tried for years to develop a culture that would produce hair cells on demand, but had little success. Corwin said the trick in his technique is to first allow the supporting cells to develop a mesenchymal phenotype, in which they adhere to the culture dish. Then, dissociating them from the dish and keeping them agitated, the cells will adhere to one another and produce hair cells.

Corwin said he was also surprised at how similar the hair cells were to those in vivo: they include one kinocilium (a true cilium that each hair cell displays) and are full of actin.

It is not yet clear whether the hair cells function normally and possess all the same machinery as those in vivo. Corwin and Hu applied FM1-43, a dye that enters through open mechanotransduction channels in hair cells, and found the cultured hair cells "lit up," indicating the dye was making it into the cell.

"FM1-43 is pretty good test while we're waiting" for physiology data, David Corey at Harvard Medical School told The Scientist. "These cells have gone a long way to becoming hair cells, and probably are [functional] hair cells."

If so, the technique "provides a huge valuable tool for people who want to use easy preparations of tissue," Stone said. Currently, obtaining hairs cells is a relatively labor-intensive process that provides extremely small amounts of hair cells-usually just a few hundred per inner ear.

Such low abundance has stymied attempts to tease out the molecular machinery of hair cell sensory transduction and the proteins that comprise it. Corey said a culture system would allow for siRNA experiments to parse the function and identity of these components.

The cells Corwin cultured came from the chick utricle, which is part of the vestibular system, not hearing. While vestibular and hearing hair cells share most of the same properties, Tony Ricci at Stanford University pointed out there are differences, such as the types of potassium channels they possess. "It will be a very nice model system to try to figure out what makes a hair cell specialized to different response properties," Ricci told The Scientist.

Ricci and others are eager to see whether this culture will hold up in mammals. It could have "a lot of value for people who are interested in developing therapies for hearing loss," Stone said. Understanding the signals that drive supporting cells to produce hair cells could provide opportunities for capitalizing on that regenerative capacity.

"Supporting cells are really the key to replacing hair cells," said Corwin. "Birds, fish, amphibians are all able to replace hair cells that are lost or damaged and recover hearing or loss of balance." Human supporting cells, however, have not demonstrated the ability to produce hair cells. Corwin said a main focus of his lab is to figure out why, and this culture is intended to aid his efforts.

Corwin said he'll be working to scale up the process and standardize it so other labs can take advantage of the culture. "Many things need to be done," Corwin said. "This is just the first report."


By Kerry Grens
mail@the-scientist.com

Links within this article:

M. Stephen, "Listen up," The Scientist, May 10, 2004.
http://www.the-scientist.com/article/display/14661/

Z. Hu and J. T. Corwin, "Inner ear hair cells produced in vitro via a mesenchymal-to-epithelial transition," PNAS, September 25, 2007.
http://www.pnas.org

Jennifer Stone
http://faculty.washington.edu/stoner

Jeffrey Corwin
http://www.healthsystem.virginia.edu/internet/corwin-lab/
J. T. Corwin and D. A. Cotanche, "Regeneration of sensory hair cells after acoustic trauma," Science, 240:1772-4, 1998.
http://www.the-scientist.com/pubmed/3381100

M. M. Stephen, "Making sense of mechanosensation," The Scientist, May 10, 2004.
http://www.the-scientist.com/article/display/14662

David Corey
http://www.fas.harvard.edu/~biophys/David_P_Corey.htm

C. Tran, "Mistaken identity in mechanotransduction," The Scientist, December, 2006.
http://www.the-scientist.com/article/display/36680

Tony Ricci
http://med.stanford.edu/ohns/faculty/ricci.html

T. Toma, "Recipe for hearing cells," The Scientist, October 28, 2003.
http://www.the-scientist.com/article/display/21734/