| Abstract: |
Human embryonic stem (hES) cells provide a potentially unlimited source of cells for brain repair. A major challenge has been to harness the enormous random differentiation potential of hES cells towards the generation of specialized cell types of therapeutic relevance. Recently, neural differentiation of hES cells has been obtained using embryoid body (EB) based differentiation strategies or selective transfer of spontaneously differentiating hES cells. However, both techniques have yielded differentiation into primarily glutamatergic and GABAergic neurons as well as astrocytes. No significant numbers of dopaminergic (DA), cholinergic or serotonergic neurons were reported.) Here we present data on the neural differentiation of hES using the inductive effects of various wild-type and transgenic stromal feeders. In combination with sequential growth factor regimens including SHH, FGF8, AA and BDNF we were able to achieve efficient DA differentiation. HES-derived dopamine neurons co-express express midbrain specific markers such as Nurr1 and Lmx1b and exhibit KCL evoked DA release. Further in vitro and in vivo characterizations are ongoing. |
