RT Journal Article SR Electronic T1 Enhanced In Vitro Midbrain Dopamine Neuron Differentiation, Dopaminergic Function, Neurite Outgrowth, and 1-Methyl-4-Phenylpyridium Resistance in Mouse Embryonic Stem Cells Overexpressing Bcl-XL JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 843 OP 852 DO 10.1523/JNEUROSCI.3977-03.2004 VO 24 IS 4 A1 Jae-Won Shim A1 Hyun-Chul Koh A1 Mi-Yoon Chang A1 Eun Roh A1 Cha-Yong Choi A1 Young J. Oh A1 Hyeon Son A1 Yong-Sung Lee A1 Lorenz Studer A1 Sang-Hun Lee YR 2004 UL http://www.jneurosci.org/content/24/4/843.abstract AB Embryonic stem (ES) cells provide a potentially unlimited source of specialized cells for regenerative medicine. The ease of inducing stable genetic modifications in ES cells allows for in vitro manipulations to enhance differentiation into specific cell types and to optimize in vivo function of differentiated progeny in animal models of disease. We have generated mouse ES cells that constitutively express Bcl-XL, an antiapoptotic protein of Bcl-2 family. In vitro differentiation of Bcl-XL overexpressing ES (Bcl-ES) cells resulted in higher expression of genes related to midbrain dopamine (DA) neuron development and increased the number of ES-derived neurons expressing midbrain DA markers compared with differentiation of wild-type ES cells. Moreover, DA neurons derived from Bcl-ES cells were less susceptible to 1-methyl-4-phenylpyridium, a neurotoxin for DA neurons. On transplantation into parkinsonian rats, the Bcl-ES-derived DA neurons exhibited more extensive fiber outgrowth and led to a more pronounced reversal of behavioral symptoms than wild-type ES-derived DA neurons. These data suggest a role for Bcl-XL during in vitro midbrain DA neuron differentiation and provide an improved system for cell transplantation in a preclinical animal model of Parkinson's disease.