In Parkinson’s disease (PD), neurodegeneration is largely confined to one discrete group of nerve cells that produce the chemical dopamine (DA). Since the death of most DA neurons almost always precedes diagnosis, cell replacement remains especially attractive as a treatment strategy for PD. Towards this end, a variety of cell sources have been studied in animal models of PD, among which human embryonic stem cells (hES) is one of the most promising. Theoretically, hES cells can generate all cell types in the body, including midbrain DA neurons. And indeed a fraction of hES cells do develop into functional DA neurons both in the tissue culture dish and after transplantation into the rat brain. A major remaining obstacle to this approach however is the continued presence of other unwanted cell types in the graft.
Our lab has recently discovered genetic markers which identify, at an early stage, those hES cells which are destined to become DA neurons. Since these cells also express unique proteins on their cell surface, it should be possible to segregate these cells from other undesirable cell types. Therefore, with the support of the Michael J. Fox Foundation, we hope to select and enrich prospective DA neurons and study their functionality after transplantation into rats with a PD lesion.