The Svendsen Laboratory
Faculty > Clive N. Svendsen
Clive N. Svendsen
Professor, Anatomy & Neurology
svendsen@waisman.wisc.edu
Organ System/Disease Focus
Parkinson’s disease, ALS, Huntington’s disease, Down syndrome
Aligned Research Focus
Genome arrays, disease modeling, aging
Research Description
We focus on the growth and differentiation of human neural stem cells derived from either fetal tissues or embryonic stem cells. The work falls into two main categories.
On the basic science front, we are interested in better defining human neural stem cells through exploring their potential for both proliferation (Wright et al, 2006) and their capacity to generate astrocytes, neurons and oligodendrocytes following differentiation (Ostenfeld and Svendsen, 2004; Suzuki et al, 2004; Nelson and Svendsen, 2006).
We are also isolating neural stem cells from patient tissues (Bahn et al, 1999) or modifying the cells to express genes involved with specific diseases in order to provide a cellular source for modeling and drug screening (Jakel et al, 2004; Schneider et al, 2007).
On the translational front, we have shown that neural stem cells derived from fetal tissues can survive transplantation into a variety of disease models (Svendsen et al, 1996; Ostenfeld et al, 2000; McBride et al, 2004). Powerful growth factors such as GNDF may have regenerative effects for patients with Parkinson’s disease (Gill et al, 2003) and ALS.
Our current experiments focus on using human neural stem cells to deliver these large proteins, which are normally screened out by the blood brain barrier, to the brain (Klein et al, 2005; Behrstock et al, 2006).
Furthermore, we hope that the astrocytes the stem cells produce may have additive effects on neuronal survival in these models of degenerative diseases and will pave the way for future clinical trials in this area (Svendsen and Langston, 2004).
Selected References
Suzuki M, McHugh J, Tork C, Shelley B, Klein SM, Aebischer P, Svendsen CN. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS ONE. 1;2(1):e689. 2007.
Schneider BL, Seehus CR, Capowski EE, Aebischer P, Zhang SC, Svendsen CN. Over-expression of alpha-synuclein in human neural progenitors leads to specific changes in fate and differentiation. Hum Mol Genet. 15;16(6):651-66. 2007.
Wright LS, Prowse KR, Wallace K, Linskens MH, Svendsen CN. Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro. Exp Cell Res. 1;312(11):2107-20. 2006.
Behrstock S, Ebert A, McHugh J, Vosberg S, Moore J, Schneider B, Capowski E, Hei D, Kordower J, Aebischer P, Svendsen CN. Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates. Gene Ther. 13:379-88. 2006.
Suzuki M, Wright LS, Marwah P, Lardy HA, Svendsen CN. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. PNAS 101:3202-3207. 2004.