The NIDCD held a workshop to explore the feasibility of reparative restoration of auditory and vestibular function. The purpose of the workshop was to discuss and identify potential areas of the auditory and vestibular systems that might be good candidates for applications being used in other reparative medicine systems, one being the potential use of stem cell biology. The workshop panel was composed of a diverse group of experts from auditory and vestibular systems as well as tissue engineers using aspects of stem cell biology in other reparative systems. The workshop was organized by Nancy Freeman, Ph.D., Division of Extramural Research, NIH-NIDCD and was chaired by Jeffrey Corwin, Ph.D., University of Virginia School of Medicine.
The meeting began at 8:30 a.m. with opening remarks from NIDCD director James Battey, Jr., M.D., Ph.D., who welcomed the panelists and attending guests. Dr. Freeman then made opening remarks, stating the reasoning and purpose for the workshop. She informed the group this workshop was not the forum to discuss ethical or developmental differences regarding stem cells themselves, but rather to focus attention on identifying and assessing areas of auditory and vestibular research potentially primed for reparative applications. Following the brief opening remarks, Dr. Jeffrey Corwin chaired and moderated the day's agenda and discussion period.
The program agenda was specifically designed for a diverse group of scientists to come together, share their research interests, and discuss the reality of applications to the auditory and vestibular systems. Each speaker was given a 45-minute time slot that included 10 minutes for questions. The 10 minutes for questions far exceeded the allotted time as there was generally a wealth of discussion following each of the presentations. Following the concluding remarks of the last speaker, a general discussion period was held to identify specific research opportunities and are highlighted below. The workshop adjourned at 5:30 p.m.
- Existence of auditory and vestibular progenitor cells.
- Identification of stem or progenitor cells that give rise to hair cells/supporting cells in embryos and adults (human).
- Determination of the origin of regenerated hair cells from reserve stem cells or through dedifferentiation of other cells.
- Determination of support cell involvement in the generation of hair cells.
- Investigation of the otic placode as one possible beginning source to identify progenitors, although cells are already developmentally biased.
- Lineage relationships of auditory and vestibular cells; potential progenitors, supporting cells, etc. Lineage development from otic placode to the terminally differentiated sensory apparatus.
- Molecular commonalities and other sources of cells.
- Usage of adult stem cells from other tissue systems (mesenchymal stem cells, hematopoietic stem cells, neural stem cells, etc.) to regenerate hair cells in vitro and/or in vivo.
- Acceptance of other cell sources for functional integration, and identification of molecules and agents that impact this.
- Usage of cochlear cells in conjunction with cochlear devices.
- Establishment of human cell lines from embryonic ear tissue.
- The auditory and vestibular microenvironment.
- Identification of agents or conditions required to stimulate cells capable of differentiating/dedifferentiating into hair cells.
- Characterization of the extracellular matrix components that control the stability or expansion of hair cells.
- Identification of new cell surface markers for progenitor cells using non-traditional probe generating techniques.
- Characterization of cell-cell interactions involved in stabilizing hair cell-support cell interactions.
- Identification of agents or conditions that repress the expansion of cochlear or vestibular structures.
- Establishment of organ culture systems of animal explants capable of regenerating hair cells to screen for agents or conditions that stimulate or repress hair cell development.
- Elucidation of growth conditions and factors that allow in vitro and in vivo propagation.
- Continuation of gene expression profiling and proteomics of the auditory sensory epithelia.
- Physiological assays.
- Detection of biochemical markers and used in combination with physiological assays demonstrating function.
- Identification and measurement of biological functions of supporting cells.
- Elucidation of essential functions for maintenance of neighboring hair cells.
- Determination of functions contributing directly or indirectly to sensory transduction in the auditory end organs.
- Determination of functions that influence the neuronal constituents of the sensory epithelia.
- Development of cell lines representative of the sensory epithelia and other otic tissues for drug screening.
- Vector and delivery systems.
- Elucidation of in vitro conditions to reform 3-dimensional arrays of cells that mimic auditory or vestibular structures.
- Technical and methodological systems to introduce stem cells into cochlear or vestibular cell arrays to regenerate hair cells (microinjection, cell targeting, or other approaches).
- Development of surgical approaches for delivery of cells or other agents into putative target area(s).
- Feasibility studies to explore accessibility for cellular replacement within the auditory and vestibular systems.
- Exploration of putative target areas: hair cell regeneration and neural restoration.
- Auditory epithelia
- Vestibular epithelia
- Spiral ganglia
- Stria vascularis
- Model systems.
- Potential use of existing transgenic models.
- Determination of the molecular basis for species-specific differences in hair cell regeneration and reparation capabilities and overall relevance to humans.
- Examination of human ear biology. Determination of limited or stimulated regeneration occurring in mammals. Retention of the molecular machinery to generate repair.
- Funding and training opportunities.
- Provision of short course (Woods Hole, Cold Spring Harbor) for hands-on instruction in methodologies unique to research in auditory and vestibular biology.
- Rapid peer review (Institute review panel) for small grants exploring new cell therapy or tissue engineering strategies for otolaryngologic reconstructions.
- Training opportunities for residents in surgical/clinical specialties of otolaryngology for tissue engineering research.