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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bohl, Delphine Liu, Song Blanchard, Stéphane Hocquemiller, Michaël Haase, Georg Heard, Jean-Michel |
| Description | Country affiliation: France Author Affiliation: Bohl D ( Département Neuroscience, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale U622, Unité Rétrovirus et Transfert Génétique, Paris, France. dbohl@pasteur.fr) |
| Abstract | Stem cell-based therapies hold therapeutic promise for degenerative motor neuron diseases, such as amyotrophic lateral sclerosis, and for spinal cord injury. Fetal neural progenitors present less risk of tumor formation than embryonic stem cells but inefficiently differentiate into motor neurons, in line with their low expression of motor neuron-specific transcription factors and poor response to soluble external factors. To overcome this limitation, we genetically engineered fetal rat spinal cord neurospheres to express the transcription factors HB9, Nkx6.1, and Neurogenin2. Enforced expression of the three factors rendered neural precursors responsive to Sonic hedgehog and retinoic acid and directed their differentiation into cholinergic motor neurons that projected axons and formed contacts with cocultured myotubes. When transplanted in the injured adult rat spinal cord, a model of acute motor neuron degeneration, the engineered precursors transiently proliferated, colonized the ventral horn, expressed motor neuron-specific differentiation markers, and projected cholinergic axons in the ventral root. We conclude that genetic engineering can drive the differentiation of fetal neural precursors into motor neurons that efficiently engraft in the spinal cord. The strategy thus holds promise for cell replacement in motor neuron and related diseases. Disclosure of potential conflicts of interest is found at the end of this article. |
| File Format | HTM / HTML |
| ISSN | 10665099 |
| Issue Number | 10 |
| Volume Number | 26 |
| e-ISSN | 15494918 |
| Journal | STEM CELLS |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2008-10-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Cell Biology Discipline Embryology Directed Molecular Evolution Genetic Engineering Motor Neurons Cytology Metabolism Stem Cells Animals Axons Biological Markers Cell Communication Cell Differentiation Cell Movement Choline Coculture Techniques Humans Mice Muscle Fibers, Skeletal Organ Specificity Rats Spinal Cord Injuries Pathology Spinal Nerve Roots Stem Cell Transplantation Transcription Factors Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Medicine Molecular Medicine |
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