29 Jan 2002

The growth and development of transplantable neurons from embryonic stem (ES) cells could potentially have immense value for those suffering from neurodegenerative diseases. But many hurdles stand in the way, not least being the transfer of what has been learned from animal models to humans. On this score, encouraging news comes from Yoshiki Sasai and colleagues at Kyoto University, who report in today's online version of the Proceedings of the National Academy of Sciences that they have been able to generate dopaminergic primate neurons using a methodology that was developed for rodent cells.

Previously the researchers found that mouse stromal cells (PA6 cells) express on their surface a neuralizing activity that induces the differentiation of ES cells into neurons (Kawasaki et al., 2000). They have now used this stromal cell-derived inducing activity (SDIA) to generate dopaminergic neurons from Cynomolgus monkey ES cells.

This technique is simple and efficient, the authors write. ES cells grown on a layer of PA6 cells differentiate within two weeks. 45 and 25 percent of differentiated cells expressed the neural markers NCAM, and class III b-tubulin, respectively. Furthermore, 80 percent of the cell colonies contained tyrosine hydroxylase-positive (TH+) dopaminergic neurons, which released dopamine when challenged with a depolarizing stimulus. These neurons had CNS characteristics, being negative for the PNS marker peripherin. When transplanted into mouse striatum, 8 percent of the cells survived and had extended neurites two weeks later, suggesting they may be viable in vivo.

"This looks very promising that the findings in the mouse can be translated into primates," said Curt Freed, University of Colorado "That is no small feat, particularly with embryonic stem cells where the conditions for growing human cells are very different."

The Japanese group is now attempting to transplant the cells into monkey brain to evaluate long-term survival of the TH+ neurons.—Tom Fagan