Kwang-Soo Kim
Molecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, Belmont, MA 02420
e-mail: kskim@mclean.harvard.edu
Because of their ability to proliferate and to differentiate into diverse cell types, ES cells are a potential source of cells for transplantation therapy of various diseases including PD. In PD, A9 dopaminergic (DA) neurons of the substantia nigra (SN) are subject to selective degeneration, whereas other DA neurons are largely spared, suggesting that A9 DA neurons are conceivably more desirable for cell-based replacement therapy of PD. Therefore, an important issue is how to establish the procedures/methods to efficiently direct the differentiation of ES cells to the A9 DA neuronal fate. Another critical issue is how to eliminate undifferentiated cells, which even in low numbers could result in teratoma/tumor formation in the host brain. A potentially efficient solution is to purify the desired cell types and to remove the undifferentiated cells before transplantation. To achieve these goals, we have combined both optimized cell culture procedures, co-culture methods, and genetic manipulation and selection methods. Finally, these principles need to be applied to either immunologically tolerable or nuclear transfer human ES cells for clinical application. These important factors will be broadly discussed in both scientific and clinical aspects.