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Clive. N. Svendsen
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 Interest in stem cell biology has exploded over the last few years. This is due to the remarkable possibilities they hold with regard to providing a source of tissues for in vitro studies, and repairing damaged tissues following disease or trauma. The Stem Cell Research Program is focused on (i) understand the molecular mechanisms responsible for their proliferation and differentiation and (ii) assess their safety and efficacy following transplantation. Until recently the thought of repairing the damaged brain was inconceivable. We are born with a certain number of neurons, and then gradually lose them through aging or disease. Or at least that was the dogma. Challenging new research suggests that the brain may be far more "plastic" than we ever imagined. New cells are accepted and allowed to grow in the adult brain, replacing old ones. New neurons are born throughout life in some brain areas. Novel growth factors can act as "fertilizer" in the brain, encouraging sick and old neurons to regenerate and function again. The challenge now is to tap into this new image of the brain through innovative approaches to treating neurological disease. We are committed to using alternative cellular sources through the generation of neural stem cells. We have extensive experience in the growth and differentiation of human neural stem cells. These are remarkably plastic and able to integrate into the developing, adult and injured brain. They also provide a unique "window" into human neural development, normally impossible to study in detail. Our labs use novel molecular and cellular techniques and detailed transplantation programs to assess function. We are also developing a gene expression profile of these cells based on gene micro-array analysis. In combination with the clinical biomanufaturing facility at the Waisman Center we are developing neural stem cell banks. We hope one day that the basic science might be moved forward to the clinic.
Svendsen, C.N., Caldwell, M.A, Shen, J. ter Borg, M.G., Rosser, A.E., Tyers, P., Karmiol, S. and Dunnett, S.B. (1997) Long term survival of human central nervous system progenitor cell transplanted into a rat model of Parkinson's Disease. Experimental Neurology,148:135-146 Ciccolini, F. and Svendsen, C.N. (1998) FGF-2 promotes acquisition of EGF responsiveness in mouse striatal precursor cells: Identification of neuronal precursor cells responding to both EGF and FGF-2. J. Neuroscience, 18: 7869-7880. Svendsen, C.N. and Smith, A.G. (1999) New prospects for human stem cell therapy in the nervous system. Trends Neurosci. 22:357-364. Ostenfeld, T., Caldwell, M.A., Prowse, K.R., Linskens, M.H., Jauniaux, E. and Svendsen, C.N. (2000) Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Experimental Neurology, 164: 215-226 Caldwell M. A., He X., Wilkie N., Pollack S., Marshall G., Wafford K. A., and Svendsen C. N. (2001) Growth factors regulate the survival and fate of cells derived from human neurospheres. Nat Biotechnol 19, 475-479. Bahn S., Mimmack M., Ryan M., Caldwell M. A., Jauniaux E., Starkey M., Svendsen C. N., and Emson P. (2002) Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down's syndrome: a gene expression study. Lancet 359, 310-315. Wu, P. , Ye, Y., Svendsen, C.N. (2002) Transduction of human neural progenitor cells using recombinant adeno-associated viruses. Gene Ther. 9, 245-255. Ostenfeld T., Joly E., Tai Y. T., Peters A., Caldwell M., Jauniaux E., and Svendsen C. N. (2002) Regional specification of rodent and human neurospheres. Brain Res Dev Brain Res 134, 43-55. Ostenfeld T., Tai Y. T., Martin P., Deglon N., Aebischer P., and Svendsen C. N. (2002) Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. Journal of Neuroscience Research 69, 955-965. Gill, S. S., Patel, N. J., Hotton, G. R., O’Sullivan, K., McCarter, R., Bunnage, M., Brooks, D. J., Svendsen, C. N. and Heywood, P. (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nature Medicine 69, 589-595 Wright, L.S., Li, J., Caldwell, M. A., Wallace, K., Johnson, J. A., and Svendsen, C. N. (2003) Gene expression in human neural stem cells: effects of leukemia inhibitory factor. J. Neurochem. 86, 179-195.
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9/15/2005 by rowley@waisman.wisc.edu
