In the last year, we have achieved a major milestone by showing that it is possible to generate functional inner ear sensory cells (hair cells) from mouse embryonic stem cells using a guidance protocol that was completely conducted in vitro (in cell culture). The goal of this project is to achieve the same result with human cells at the end of the funding period. We are on track with this endeavor, but we have encountered a number of quite substantial roadblocks. The major roadblock is that human cells appear to require much more time to differentiate into mature inner ear cell types when compared with mouse cells. We are currently working on a protocol that allows us to provide a sustained stimulation of the cell signaling pathways that are needed to keep human cells on track to develop along the otic (inner ear) pathway. We have learned a lot about how human embryonic stem cells react when exposed to various signaling environments and we have made the discovery that the embryonic stem cells are able to differentiate relatively quickly into early embryonic cells (lineages), but that the development of later cell types (i.e. organogenesis), does require quite some time.