Year 1

A promising strategy to treat neurodegenerative diseases is to use embryonic stem cell (ESC)-derived neurons to replace damaged or diseased populations of neurons. In our CIRM-funded studies, we proposed to establish a protocol that will derive spinal sensory interneurons (INs) from ESCs. These INs are required to reestablish the sensory connections that would allow an injured patient to perceive external stimuli, such as pain and temperature. The existence of in vitro derived spinal sensory INs would also accelerate studies examining the basis of debilitating spinal dysfunctions, such as congenital pain insensitivity.

We have made significant progress towards this goal in year 1. We have identified that specific members of the Bone Morphogenetic Protein (BMP) family can direct mouse ESCs towards specific classes of spinal INs. These signals appear to be evolutionally conserved: our preliminary results suggest that BMPs have the same activity directing human ESCs towards spinal sensory IN fates. We are thus well poised to initiate our proposed studies in year 2: assessing whether stem cell derived INs can integrate in the spinal cord.