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TISSUE-SPECIFIC STEM CELLS

Noninvasive and Quantitative Monitoring of Adult Neuronal Stem Cell Migration in Mouse Brain Using Bioluminescence Imaging

Laboratories for ^aNeurobiology and Gene Therapy and
^bMolecular Virology and Gene Therapy, Division of Molecular Medicine, and
^cDivision of Nuclear Medicine,
^dMolecular Small Animal Imaging Center (MoSAIC), Katholieke Universiteit Leuven, Leuven, Flanders, Belgium

Key Words. In vivo optical imaging • Neural stem cells • Gene transfer • Lentiviral vectors • Growth factors

Correspondence: Correspondence: Veerle Baekelandt, Ph.D., Kapucijnenvoer 33, B-3000 Leuven, Belgium. Telephone: 32-16-33-36-32; Fax: 32-16-33-63-36; e-mail: veerle.baekelandt{at}med.kuleuven.be

Received on December 13, 2007; accepted for publication on June 11, 2008.

First published online in STEM CELLS EXPRESS  July 3, 2008.

It is now generally accepted that continuous neurogenesis occurs in the adult mammalian brain, including that of humans. Modulation of adult neurogenesis can provide therapeutic benefits for various brain disorders, including stroke and Parkinson's disease. The subventricular zone-olfactory bulb pathway is one of the preferred model systems by which to study neural stem cell proliferation, migration, and differentiation in adult rodent brain. Research on adult neurogenesis would greatly benefit from reliable methods for long-term noninvasive in vivo monitoring. We have used lentiviral vectors encoding firefly luciferase to stably mark endogenous neural stem cells in the mouse subventricular zone. We show that bioluminescence imaging (BLI) allows quantitative follow-up of the migration of adult neural stem cells into the olfactory bulb in time. Moreover, we propose a model to fit the kinetic data that allows estimation of migration and survival times of the neural stem cells using in vivo BLI. Long-term expression of brain-derived neurotrophic factor in the subventricular zone attenuated neurogenesis, as detected by histology and BLI. In vivo monitoring of the impact of drugs or genes on adult neurogenesis is now within reach.

Disclosure of potential conflicts of interest is found at the end of this article.

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