[Frontiers in Bioscience E4, 1170-1181, January 1, 2012]

Genetically modified stem cells for the treatment of neurological diseases

Dinko Mitrecic1, Charles Nicaise2, Lars Klimaschewski3, Srecko Gajovic1, Delphine Bohl4, Roland Pochet2

1Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 12, HR-10000 Zagreb, Croatia, 2Laboratory of Histology, Neuroanatomy and Neuropathology, Universite Libre de Bruxelles, 808 route de Lennik, 1070 Bruxelles, Belgium 3Division of Neuroanatomy, Medical University of Innsbruck, Muellerstrasse 59, A-6020 Innsbruck, Austria 4Unite Retrovirus et Transfert Genetique, INSERM U622, Departement de Neuroscience, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Genetic modifications as a tool to obtain stem cells
4. Neuronal differentiation of stem cells
5. Genetically modified cells for the treatment of neurodegenerative diseases
5.1. Neurodegenerative diseases
5.2. Parkinson's disease
5.3. Amyotrophic lateral sclerosis
5.4. Huntington's disease
5.5. Alzheimer's disease
6. Genetically modified cells for the treatment of stroke
7. Genetically modified stem cells for treatment of axonal damage
8. Genetically modified cells for treatment of other neurological diseases
9. Conclusion
10. Acknowledgements
11. References

1. ABSTRACT

The central nervous system has a very poor regenerative potential and is difficult to access. This partly explains why neurological diseases often lack appropriate therapeutic options and represent the most significant burden for healthcare systems. Progress in understanding the molecular background of neurological diseases requires innovative approaches offering new hope for the patients. One of the most intriguing and promising options is the combination of stem cells with gene therapy. Unlike fibroblasts, stem cells exhibit a high tropism for disease-affected tissue and integrate into the nervous tissue. This makes them ideal candidates for the production and delivery of molecules of interest for treating the nervous system. This article reviews the methodology for obtaining pluripotent stem cells (iPSCs) as precursors for neuronal cells, glial cells and the current state of the art in applications of genetically modified stem cells in animal models of neurodegenerative diseases, stroke, axonal damage, tumors and epilepsy.