Original Article
Gene Therapy (2007) 14, 118–128. doi:10.1038/sj.gt.3302847; published online 31 August 2006
Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells
J R Pineda1, N Rubio2, P Akerud3, N Urbán1, L Badimon2, E Arenas3, J Alberch1, J Blanco2 and J M Canals1
- 1Departament de Biologia Cel
lular i Anatomia Patològica, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, Barcelona, Spain - 2Cardiovascular Research Center, ICCC-CSIC, Hospital de Sant Pau, Barcelona, Spain
- 3Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Correspondence: Dr JM Canals, Departament de Biologia Cel
lular i Anatomia Patològica, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, C/Casanova, 143, E-08036 Barcelona, Spain. E-mail: jmcanals@ub.edu
Received 16 February 2006; Revised 10 July 2006; Accepted 10 July 2006; Published online 31 August 2006.
Abstract
The use of stem cells for reconstructive or neuroprotective strategies can benefit from new advances in neuroimaging techniques to track grafted cells. In the present work, we analyze the potential of a neural stem cell (NSC) line, which stably expresses the glial cell line-derived neurotrophic factor (GDNF) and the firefly luciferase gene (GDNF/Luc-NSC), for cell therapy in a Huntington's disease mouse model. Our results show that detection of light photons is an effective method to quantify the proliferation rate and to characterize the migration pathways of transplanted NSCs. Intravenous administration of luciferine, the luciferase substract, into the grafted animals allowed the detection of implanted cells in real time by an optical neuroimaging methodology, overpassing the limits of serial histological analyses. We observed that transplanted GDNF/Luc-NSCs survive after grafting and expand more when transplanted in quinolinate-lesioned nude mouse striata than when transplanted in non-lesioned mice. We also demonstrate that GDNF/Luc-NSCs prevent the degeneration of striatal neurons in the excitotoxic mouse model of Huntington's disease and reduce the amphetamine-induced rotational behavior in mice bearing unilateral lesions.
Keywords:
neurodegenerative disorders, striatum, cell grafting, neurotrophic factors, neuroprotection, non-invasive imaging
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