MANIPULATION OF SHC(s) MOLECULES TO OPTIMIZE STEM CELLS EMPLOYMENT FOR CELL REPLACEMENT IN THE MAMMALIAN BRAIN

Identification of neural stem cell in the embryonic and adult brain, followed by the development of strategies fo their grouth in vitro, has opened great prospectives for brain neurodegenerative disorders. These cells can indeed be utilized for cell replecement strategies and ex-vivo gene therapy to the brain. However several aspects of their biological properties and differentiative abilities remain unexplained. As an example, transplantation of Neural Stem Cells into the adult brain mainly lead to astrocytes. Improving the ratio of neurons over glial cells obtained from Neural Stem Cells is therefore an important task. Based on our knowledge on the presence and activities of the Shc(s) molecules in the developing and mature brain, we aim at modifying the levels of the Shc(s) in the cells to improve their neuronal differentiation. We have previously demonstrated that ShcA protein is present in neuronal progenitor cells while ShcC is present in postmitotic mature neurons (Conti 1997, 2001). This project has the aim to apply these knowledge to control proliferation and differentiation of NSC in vitro, results which may be of interest for NSC-based cell and gene therapy strategies.