Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cells
| Autor: | Anne Elizabeth Rosser, Alastair Compston, William F. Blakemore, Siddharthan Chandran, Maeve A. Caldwell, Karen-Amanda Irvine, Colin Watts, Daniel J. Webber, Nicholas D. Allen, Alexis J Joannides, Claire Kelly, Olivier Raineteau, Paul J. Kemp |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Central Nervous System
Cellular differentiation Clinical uses of mesenchymal stem cells Biology Rats Mutant Strains Cell Line Mice Animals Humans Cell Lineage Progenitor cell Embryonic Stem Cells reproductive and urinary physiology Neurons Microscopy Confocal Multipotent Stem Cells Cell Differentiation Immunohistochemistry Embryonic stem cell Neural stem cell Nerve Regeneration Rats Electrophysiology Neuroepithelial cell nervous system Astrocytes Brain Injuries Neurology (clinical) biological phenomena cell phenomena and immunity Stem cell Neuroglia Neuroscience Stem Cell Transplantation Adult stem cell |
| Zdroj: | Brain. 130:1263-1275 |
| ISSN: | 1460-2156 0006-8950 |
| Popis: | Human embryonic stem cells (hESCs) are a potential source of defined tissue for cell-based therapies in regenerative neurology. In order for this potential to be realized, there is a need for the evaluation of the behaviour of human embryonic stem cell-derived neural stem cells (hES-NSCs) both in the normal and the injured CNS. Using normal tissue and two experimental models, we examined the response of clinically compatible hES-NSCs to physiological and pathological signals. We demonstrate that the phenotypic potential of a multipotent population of hES-NSCs is influenced by these cues both in vitro and in vivo. hES-NSCs display a temporal profile of neurogenic and gliogenic differentiation, with the generation of mature neurons and glia over 4 weeks in vitro, and 20 weeks in the uninjured rodent brain. However, transplantation into the pathological CNS accelerates maturation and polarizes hES-NSC differentiation potential. This study highlights the role of environmental signals in determining both lineage commitment and temporal maturation of human neural stem cells. Controlled manipulation of environmental signals appropriate to the pathological specificity of the targeted disease will be necessary in the design of therapeutic stem cell-based strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|