Funding opportunities

Hair Cells and Spiral Ganglion Neuron Differentiation from Human Embryonic Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
Principle Investigator: 
Funds requested: 
$469 327
Funding Recommendations: 
Recommended if funds allow
Grant approved: 
Public Abstract: 
Statement of Benefit to California: 
Review Summary: 
The applicant proposes to study the potential of hESC to differentiate into hair cells and spiral ganglion neurons. They will initially study cochlear explant cultures and dissociated hESCs and then assess the role of interacting signalling proteins and transcription factors that have been identified as having roles in differentiation of hair cells. SIGNIFICANCE AND INNOVATION: There is no doubt that achieving large numbers of auditory hair cell precursors from hES cells would be truly important toward a goal of replacement approaches for loss of these cells from aging or noise damage. Proof of principle of the generation of significant numbers of any peripheral sensory neuron population would be extremely significant. This is an innovative and original proposal. STRENGTHS: This is a very strong proposal from a uniquely qualified group, using an in vitro preparation to assess the interactions of differentiated hESC cells with cultured hearing/vestibular organs, hence avoiding the problem of immune-rejection and other systemic effects. They will be focusing on rational design of a cocktail of protein/factors that can be used for such implants. This study is very likely to yield important insights into factors that affect differentiation, proliferation, development, and hESC signalling. WEAKNESSES: It should be assumed that it is not that going to be that easy to achieve directed differentiation of hair cells from hESCs. The applicant has no documented expertise in the ability to achieve this, and one co-worker does have some expertise with cell proliferation and differentiation studies of rodent inner ear epithelial cell cultures, but not with hES cell culturing. Aim 1 alone, with focus on the right population of hES cells that could give rise to hair cells, could monopolize all of the time and effort on this project. Identification of interacting proteins and transcription factors in Aim 3, and the gene-silencing studies together make this a way-too-ambitious endeavor. DISCUSSION: There was considerable discussion about this project, with some more skeptical than others. Questions had to do with likely difficulty in generating this cell type, availability of appropriate markers/assays for desired cell type (and intermediary stages) and complexity of an electrophysiological endpoint. PROGRAMMATIC REVIEW: In programmatic review, the applicant was recognized as being a promising young investigator with an innovative proposal for work in an area that could have an impact on deafness. His application was recommended for special consideration if funding were available.

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