Adult Bone Marrow Stromal Cells in the Embryonic Brain: Engraftment, Migration, Differentiation, and Long-Term Survival
| Autor: | Guillermo Muñoz-Elias, Dale Woodbury, Ira B. Black, Akiva J. Marcus, Thomas M. Coyne |
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| Rok vydání: | 2004 |
| Předmět: |
Time Factors
Stromal cell Cell Survival Rostral migratory stream Development/Plasticity/Repair Subventricular zone Bone Marrow Cells Nerve Tissue Proteins Nestin Rats Sprague-Dawley Intermediate Filament Proteins Cell Movement medicine Animals Vimentin Cells Cultured Neurons Neuronal Plasticity biology General Neuroscience Graft Survival Mesenchymal stem cell Brain Cell Differentiation Antigens Differentiation Olfactory Bulb Frontal Lobe Rats Olfactory bulb Cell biology Phenotype medicine.anatomical_structure nervous system biology.protein Female Bone marrow Stromal Cells NeuN Neuroglia Neuroscience |
| Zdroj: | The Journal of Neuroscience. 24:4585-4595 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | We recently differentiated adult rat and human bone marrow stromal cells (MSCs) into presumptive neurons in cell culture. To determine whether the MSCs assume neuronal functionsin vivo, we now characterize for the first time engraftment, migration, phenotypic expression, and long-term survival after infusion into embryonic day 15.5 (E15.5) rat ventriclesin utero. By E17.5, donor cells formed discrete spheres in periventricular germinal zones, suggesting preferential sites of engraftment. The cells expressed progenitor vimentin and nestin but not mature neuronal markers. By E19.5, a subset assumed elongated migratory morphologies apposed to radial nestin-positive fibers running through the cortical white matter and plate, suggesting migration along radial glial processes. Cells remaining in germinal zones extended long, vimentin-positive fibers into the parenchyma, suggesting that the MSCs generated both migratory neurons and guiding radial glia. Consistent with this suggestion, >50% of cultured mouse MSCs expressed the neuroprecursor/radial glial protein RC2. From E19.5 to postnatal day 3, MSCs populated distant areas, including the neocortices, hippocampi, rostral migratory stream, and olfactory bulbs. Whereas donor cells confined to the subventricular zone continued to express nestin, cells in the neocortex and midbrain expressed mature neuronal markers. The donor cells survived for at least 2 months postnatally, the longest time examined. Confocal analysis revealed survival of thousands of cells per cubic millimeter in the frontal cortex and olfactory bulb at 1 month. In the cortex and bulb, 98.6 and 77.3% were NeuN (neuronal-specific nuclear protein) positive, respectively. Our observations suggest that transplanted adult MSCs differentiate in a regionally and temporally specific manner. |
| Databáze: | OpenAIRE |
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