Cell based therapies potentially allow for alternative treatment of several human diseases. The search for an autologous cell source merits the investigation of novel means to de-program patient derived differentiated cells into pluripotent embryonic stem (ES) cells (or ES-like cells) with therapeutic potentials. The technique of cloning by somatic cell nuclear transfer (SCNT), where a differentiated somatic cell is transferred into an enucleated oocyte has now in several mammalian species proven that the oocyte possesses factors that can entirely de- and re-program the somatic cell genome.
In this project, cytoplasmic extract of bovine oocytes obtained at the slaughterhouse will be used to de-program bovine and human granulosa cells into potential pluripotent ES-like cells. Recent data from the host laboratories indicate that the nucleolus can be used as a marker for genomic de-programming in conjunction with SCNT and that the de-programming effect of the oocyte is not species specific. Building on this back ground, we intend to use the nuclear and nucleolar architecture as well as markers of pluripotency of a somatic cell exposed to extracts from oocyte cytoplasm, to examine whether de-programming of the somatic cell genome is possible and to gain insight into the underlying molecular changes that are required to induce gene de-programming. This new knowledge generated in this research training project will constitute the basis for creating ES or ES-like cells for autologous cell replacement therapy circumventing the need for producing SCNT-embryos for ES cell derivation.
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