The sensory hair cells of the inner ear are necessary for the detection of sound and head movement. Hair cells may be lost from the inner ear as a result of noise exposure, treatment with certain drugs, or as a consequence of aging. Recent evidence has shown that hair cells can regenerate in the ears of adult birds and mammals, and that supporting cells in organ cultures of ears taken from adult humans will proliferate after the death of hair cells. These findings strongly suggest that hair cell regeneration may be induced in the ears of humans. In order to develop clinical strategies that will bring about hair cell regeneration in the human ear, it is first necessary to understand how regeneration is initiated. More specifically, we must know what cellular and molecular signals are responsible for triggering the regenerative proliferation of inner ear supporting cells after the death of hair cells, and how these cells then go on to form replacement hair cells. The goal of the proposed research is to identify factors that trigger regenerative proliferation in the ears of warm-blooded vertebrates. Experiments will be carried out that test the ability of identified mitogenic growth factors to enhance the regenerative proliferation of supporting cells in organ culture preparations of inner ear sensory epithelia taken from birds and from adult humans. Additional experiments will determine whether the vestibular sensory organs of adult birds produce a diffusible mitogenic growth factor. The role of leukocytes in the process of hair cell regeneration will also be explored. Finally, experiments will be conducted that will determine whether hair cells can also regenerate by differentiating from existing supporting cells, without any accompanying cell division.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29DC002291-06
Application #
2828564
Study Section
Hearing Research Study Section (HAR)
Project Start
1994-04-01
Project End
2000-03-31
Budget Start
1998-06-01
Budget End
2000-03-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Central Institute for the Deaf
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
Kruger, R P; Goodyear, R J; Legan, P K et al. (1999) The supporting-cell antigen: a receptor-like protein tyrosine phosphatase expressed in the sensory epithelia of the avian inner ear. J Neurosci 19:4815-27
Corwin, J T; Warchol, M E; Saffer, L D et al. (1996) Growth factors as potential drugs for the sensory epithelia of the ear. Ciba Found Symp 196:167-82;discussion 182-7