S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Dept. of Chemical and Biological Engineering (화학생물공학부) Theses (Master's Degree_화학생물공학부)
Overexpression of anti-apoptotic Bcl-XL in mouse ES cells enhances dopamine neuron differentiation with increased in vitro and in vivo functions and resistance to Parkinsonian toxin
- Issue Date
- 서울대학교 대학원
- Embryonic Stem (ES) cells; dopamine neurons; Bcl-XL; Parkinson`s disease; transplantation; differentiation
- Thesis (master`s)--서울대학교 대학원 :응용화학부,2003.
- 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
ES cells that constitutively express Bcl-XL, an anti-apoptotic protein of Bcl-2 family. In
vitro differentiation of Bcl-XL overexpressing ES cells (Bcl-ES) resulted in higher
expression of genes related to midbrain dopamine (DA) neuron development and
increased the number and function of ES-derived DA neurons compared to
differentiation of wild-type ES cells. Moreover, DA neurons derived from Bcl-ES cells
were less susceptible to 1-methyl-4-phenylpyridium (MPP+), a neurotoxin for DA
neurons. Upon 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 Parkinsons disease.
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