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Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells

Gene Therapy volume 14, pages 118–128 (2007)Cite this article

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.

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Acknowledgements

We thank M Teresa Muñoz and Ana López for technical assistance, and Dr Jaume Comas from the Cell Separation Unit of the Serveis Científico-Tècnics (Universitat de Barcelona) for their support and advice with the cell sorting procedures We thank Dr Evan Y Snyder for the generous gift of the c17.2 cell line. We are also grateful to Dr Amèrica Jiménez and the staff of the animal facility (Facultat de Medicina, Universitat de Barcelona) for their help with mice care. This study was supported by grants from the Ministerio de Educación y Ciencia (SAF2005-01335, JA; SAF2005-00147, JMC; Spain), the Ministerio de Sanidad y Consumo (Redes Temáticas de Investigación Coorporativa: G03/167 and G03/210 and FIS: PI040659; Spain), Fundació La Caixa (Spain) and the Network of excellence for Diagnostic Molecular Imaging (DiMI; Sixth Framework, European Community). JRP is a fellow from the Spanish Ministerio de Educación y Ciencia and NU is a fellow from CIRIT, Generalitat de Catalunya (Spain).

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Authors and Affiliations

  1. Departament de Biologia Cel·lular i Anatomia Patològica, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, Barcelona, Spain

    J R Pineda, N Urbán, J Alberch & J M Canals

  2. Cardiovascular Research Center, ICCC-CSIC, Hospital de Sant Pau, Barcelona, Spain

    N Rubio, L Badimon & J Blanco

  3. Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden

    P Akerud & E Arenas

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  1. J R Pineda
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  2. N Rubio
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  3. P Akerud
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  6. E Arenas
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  7. J Alberch
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  8. J Blanco
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  9. J M Canals
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Correspondence to J M Canals.

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Pineda, J., Rubio, N., Akerud, P. et al. Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells. Gene Ther 14, 118–128 (2007). https://doi.org/10.1038/sj.gt.3302847

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