Year 4

The overarching goal of this grant was to develop an experimental protocol for coaxing human embryonic stem cells to develop into inner ear sensory hair cells. This work has implications on future treatment of hearing loss and balance disorders, for which no current treatment exist. Generation of sensory hair cells and their accompanying so-called supporting cells is a complex endeavor because these cells develop from an embryonic structure called the otic placode. Generation of placodal cells is quite complex and appears not to be a default pathway, which can be explored for generation of myocytes or neural cells. Another aggravating factor was that human cells appear to require a different guidance protocol than mouse ESCs.

With 4 years of CIRM funding, we were able to overcome most of the obstacles that we encountered along the way and we are now at a point where we are able to generate human hair cell-like cells in the culture dish. These cells express appropriate marker proteins and they display the cytomorphological specializations that you would expect to find in a sensory hair cell. Still, more experiments are needed to ensure that the cells function properly. These analyses are complicated and they require an additional manipulation of human ESCs (adding a transgenic reporter). This work is still ongoing and it is required for publishing the results of the study.