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Committed Neural Progenitor Cells Derived from Genetically Modified Bone Marrow Stromal Cells Ameliorate Deficits in a Rat Model of Stroke
- Source :
- Journal of Cerebral Blood Flow & Metabolism. 29:1409-1420
- Publication Year :
- 2009
- Publisher :
- SAGE Publications, 2009.
-
Abstract
- Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid (GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.
- Subjects :
- Stromal cell
Cellular differentiation
Cell Culture Techniques
Clinical uses of mesenchymal stem cells
Bone Marrow Cells
Transfection
Neurosphere
Animals
Humans
Medicine
Cell Lineage
Receptor, Notch1
Neurons
Behavior, Animal
business.industry
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Neural stem cell
Rats
Cell biology
Stroke
Neuroepithelial cell
Disease Models, Animal
medicine.anatomical_structure
Neurology
Neurology (clinical)
Bone marrow
Stromal Cells
Cardiology and Cardiovascular Medicine
business
Neuroscience
Stem Cell Transplantation
Subjects
Details
- ISSN :
- 15597016 and 0271678X
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Accession number :
- edsair.doi.dedup.....f8d9b90b4e7420f4aa9da0e6fb8c4a59