Embryonic stem (ES) cells display a prodigious ability to differentiate into diverse cell types and are seen as a promising renewable source of specialized cells for use in regenerative medicine. Since the use of human stem cells raises ethical concerns and is tightly regulated, animal models provide a useful tool to further explore the potential of this technology. In the September 21 Nature Biotechnology, Tiziano Barberi and colleagues at the Memorial Sloan-Kettering Cancer Center demonstrate that transplantation of dopaminergic neurons derived from cloned mouse ES cells can significantly improve the condition of parkinsonian mice (Nature Biotechnology, DOI:10.1038/nbt870, September 21, 2003).

Barberi et al. developed an improved cell culture system that allowed the rapid and efficient derivation of most nervous system neural subtypes. They could selectively generate highly enriched populations of dopaminergic, serotonergic, cholinergic, and GABAergic neurons, as well as astroglia and oligodendroglia. When transplanted into the brains of mice with damaged dopamine neurons—a model of Parkinson disease—the dopamine neurons generated by cloned ES showed long-term survival and ultimately led to the correction of behavioral deficits.

That mouse ES cells can be used in cell replacement therapy in an animal model of Parkinson disease is not unprecedented. However, previous attempts relied on ES cell lines transfected with a cytomegalovirus plasmid driving expression of rat Nurr1 (a transcriptional factor involved in the differentiation of midbrain precursors into dopamine neurons) that left questions about the long-term safety of a therapeutic approach based on the use of transgenic cells.

The work by Barberi et al. is the first example of therapeutic cloning for treating brain disorders. Although this technique has the potential to treat a range of diseases, "future therapeutic applications may require extensive work to adapt our protocols to human ES cells," warn the authors.