Abstract: |
This chapter explores uses of embryonic stem cells (ESCs) aimed at modeling Parkinson's disease in vitro. ES-derived mDA neurons provide a number of advantages over embryo-derived neurons. One of the main advantages is the unlimited supply of neurons. ES-based differentiations can be scaled up to provide the required number of mDA neurons. ESCs are pluripotent, meaning they can differentiate into a wide range of cell types, and therefore a PD-related genotype can be differentiated into many different cell types in vitro. ESCs can develop into any cell of the adult organism, such as in the case of mouse ESCs. Genetically modified ESCs can be introduced into a developing mouse embryo to subject the modified cells into a partial (chimera) or complete mouse (tetraploid aggregation). Another advantage of using ESCs is the ability to precisely alter the genome of karotypically normal cells. An approach for genetic modification with ESCs is the use of conventional, plasmid-based transgenes whereby a promoter-gene-polyadenylation cassette is randomly integrated into the ESC genome. ESC-based DA neurons also provide an ideal substrate for large-scale, high-throughput screens. © 2008 Elsevier Inc. All rights reserved. |