Both the authors contributed equally to this work.
Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons
Article first published online: 9 AUG 2007
Journal of Neurochemistry
Volume 103, Issue 4, pages 1417–1429, November 2007
How to Cite
Ko, J.-Y., Park, C.-H., Koh, H.-C., Cho, Y.-H., Kyhm, J.-H., Kim, Y.-S., Lee, I., Lee, Y.-S. and Lee, S.-H. (2007), Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. Journal of Neurochemistry, 103: 1417–1429. doi: 10.1111/j.1471-4159.2007.04898.x
- Issue published online: 9 AUG 2007
- Article first published online: 9 AUG 2007
- Received April 6, 2007; revised manuscript received June 12, 2007; accepted July 2, 2007.
- dopamine neurons;
- human embryonic stem cells;
- neural precursor cell;
- Parkinson’s disease
Human embryonic stem (hES) cells can be guided to differentiate into ventral midbrain-type neural precursor (NP) cells that proliferate in vitro by specific mitogens. We investigated the potential of these NP cells derived from hES cells (hES-NP) for the large-scale generation of human dopamine (DA) neurons for functional analyses and therapeutic applications. To address this, hES-NP cells were expanded in vitro for 1.5 months with six passages, and their proliferation and differentiation properties determined over the NP passages. Interestingly, the total hES-NP cell number was increased by > 2 × 104-folds over the in vitro period without alteration of phenotypic gene expression. They also sustained their differentiation capacity toward neuronal cells, exhibiting in vitro pre-synaptic DA neuronal functionality. Furthermore, the hES-NP cells can be cryopreserved without losing their proliferative and developmental potential. Upon transplantation into a Parkinson’s disease rat model, the multi-passaged hES-NP cells survived, integrated into the host striatum, and differentiated toward the neuronal cells expressing DA phenotypes. A significant reduction in the amphetamine-induced rotation score of Parkinson’s disease rats was observed by the cell transplantation. Taken together, these findings indicate that hES-NP cell expansion is exploitable for a large-scale generation of experimental and transplantable DA neurons of human-origin.