The neurons and sensory cells of the mammalian inner ear do not regenerate once they are damaged by toxins, excessive noise, or infectious agents. The recent discovery that mouse embryonic stem (ES) cells can be induced to differentiate into sensory cells of the inner ear in vitro provides a basis for characterizing the pathways by which this development from stem cell to inner ear cell occurs. The genes that promote this differentiation will be investigated and the genes will be selectively expressed in stem cell progenitors to determine the optimal conditions for generation of hair cells and spiral ganglion neurons. An assay system will be developed that uses reporter constructs that correlate to the cellular differentiation induced by the expression of both candidate genes and a library of inner ear genes. The information will then be used to produce inner ear cells from human ES cells and the resulting cells will be candidates for transplantation. The information on differentiation will also be useful in future attempts to activate endogenous stem cells either with small molecules or by gene delivery. The long term objective is to develop therapies that can replace cells lost to degeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
National Research Service Awards for Senior Fellows (F33)
Project #
1F33DC006789-01
Application #
6792817
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2004-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
1
Fiscal Year
2004
Total Cost
$60,532
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Martinez-Monedero, Rodrigo; Oshima, Kazuo; Heller, Stefan et al. (2007) The potential role of endogenous stem cells in regeneration of the inner ear. Hear Res 227:48-52
Jeon, Sang-Jun; Oshima, Kazuo; Heller, Stefan et al. (2007) Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells. Mol Cell Neurosci 34:59-68
Martinez-Monedero, Rodrigo; Corrales, C Eduardo; Cuajungco, Math P et al. (2006) Reinnervation of hair cells by auditory neurons after selective removal of spiral ganglion neurons. J Neurobiol 66:319-31
Corrales, C Eduardo; Pan, Luying; Li, Huawei et al. (2006) Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti. J Neurobiol 66:1489-500