Abstract: |
Embryonic stem (ES) cells serve as universal building blocks for the generation of all somatic cell types including cells of the CNS. ES cells are obtained from the inner cell mass of a fertilization-derived blastocytes. Alternatively, autologous stem cells with ES properties can be obtained via nuclear transfer (ntES(1)) or parthenogenesis (pgES(2). Here we show methods for the efficient in vitro differentiation of both mouse ES and ntES cells. Progeny of ES and ntES cells were characterized by immunohistochemistry, gene expression analyses, neurotransmitter release, electrophysiology and electron microscopy. All these in vitro data confirm the neuronal and dopaminergic properties of ES and ntES derived progeny. Transplantation of ES and ntES derived dopamine neurons into PD mice yielded large grafts containing between 2,000 45,000 TH+ cells 8 weeks after transplantation. These data demonstrate the potential of ES cells in neural transplantation and provide the basis for successful therapeutic cloning in PD mice. 1. Wakayama, T., V. Tabar, I. Rodriguez, A. C. Perry, L. Studer, and P. Mombaerts. Science 292: 740-743, 2001.; 2.Cibelli, J. B., K. A. Grant, K. B. Chapman, K. Cunniff, T. Worst, H. L. Green, S. J. Walker, P. H. Gutin, L. Vilner, V. Tabar, T. Dominko, J. Kane, P. J. Wettstein, R. P. Lanza, L. Studer, K. E. Vranan, and M. D. West. Science 295: 819, 2002. |