Diseases affecting the nervous system are many, whereas effective treatments are few. Recent experimental successes with neural stem cells (NSCs) in rodent models therefore provide encouragement to those working to repair the brain, retina, and spinal cord. In our experience, as well as that of others, NSCs demonstrate an unprecedented capacity for integration into the diseased central nervous system (CNS) of mature mammals. Furthermore, it is now clear that multipotent neural precursors can be derived from post-natal sources, apparently including cadaveric human tissue. The recent development of transgenic mice expressing green fluorescent protein (GFP), either constitutively or under control of the nestin promoter (pNestin-EGFP), has enabled the derivation of NSCs pre-labeled with this marker. The studies proposed here will characterize constitutive and conditional GFP-expressing transgenic NSCs in terms of baseline production of cytokines, expression of a range of surface markers, regulatory control of surface marker expression in response to cytokine stimulation and immunogenic activity in mixed co-cultures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS044060-02
Application #
6607388
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Chiu, Arlene Y
Project Start
2002-07-05
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$161,500
Indirect Cost
Name
Children's Hospital of Orange County
Department
Type
DUNS #
796024966
City
Orange
State
CA
Country
United States
Zip Code
92868
Klassen, Henry; Warfvinge, Karin; Schwartz, Philip H et al. (2008) Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the retina of allorecipients. Cloning Stem Cells 10:391-402
Klassen, Henry; Schwartz, Philip H; Ziaeian, Boback et al. (2007) Neural precursors isolated from the developing cat brain show retinal integration following transplantation to the retina of the dystrophic cat. Vet Ophthalmol 10:245-53
Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem et al. (2007) Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients. Stem Cells 25:1222-30
Warfvinge, Karin; Kiilgaard, Jens F; Klassen, Henry et al. (2006) Retinal progenitor cell xenografts to the pig retina: immunological reactions. Cell Transplant 15:603-12
Lavik, E B; Klassen, H; Warfvinge, K et al. (2005) Fabrication of degradable polymer scaffolds to direct the integration and differentiation of retinal progenitors. Biomaterials 26:3187-96
Warfvinge, Karin; Kiilgaard, Jens F; Lavik, Erin B et al. (2005) Retinal progenitor cell xenografts to the pig retina: morphologic integration and cytochemical differentiation. Arch Ophthalmol 123:1385-93
Schwartz, Philip H; Nethercott, Hubert; Kirov, Ivan I et al. (2005) Expression of neurodevelopmental markers by cultured porcine neural precursor cells. Stem Cells 23:1286-94
Klassen, Henry; Ziaeian, Boback; Kirov, Ivan I et al. (2004) Isolation of retinal progenitor cells from post-mortem human tissue and comparison with autologous brain progenitors. J Neurosci Res 77:334-43
Klassen, Henry J; Ng, Tat Fong; Kurimoto, Yasuo et al. (2004) Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior. Invest Ophthalmol Vis Sci 45:4167-73
Klassen, Henry J; Imfeld, Karen L; Kirov, Ivan I et al. (2003) Expression of cytokines by multipotent neural progenitor cells. Cytokine 22:101-6

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