Method of inducing and maintaining neuronal cells
First Claim
1. A method for inducing a stem cell having activin receptors responsive to activin to differentiate to a neuronal cell phenotype, which stem cell is provided in a culture of two or more cells in vitro, comprising providing said cell witha first agent that antagonizes the biological action of activin selected from follistatin, proteins that include at least one follistatin module, an α
- 2-macroglobulin, and an inhibin, and a second agent which agent is a neurotrophic factor that enhances a particular differentiation fate of the cell, wherein said first agent and second agent are provided in amounts sufficient to induce differentiation of said cell to a neuronal cell phenotype.
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Abstract
The present invention makes available a method for inducing neuronal differentiation and preventing the death or degeneration of neuronal cells both in vitro and in vivo. The subject method stems from the unexpected finding that, contrary to traditional understanding of neural induction, the default fate of ectodermal tissue is neuronal rather than mesodermal and/or epidermal. In particular, it has been discovered that preventing or antagonizing a signaling pathway in a cell for a growth factor of the TGF-β family can result in neuronal differentiation of that cell.
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Citations
21 Claims
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1. A method for inducing a stem cell having activin receptors responsive to activin to differentiate to a neuronal cell phenotype, which stem cell is provided in a culture of two or more cells in vitro, comprising providing said cell with
a first agent that antagonizes the biological action of activin selected from follistatin, proteins that include at least one follistatin module, an α - 2-macroglobulin, and an inhibin, and
a second agent which agent is a neurotrophic factor that enhances a particular differentiation fate of the cell, wherein said first agent and second agent are provided in amounts sufficient to induce differentiation of said cell to a neuronal cell phenotype. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
- 2-macroglobulin, and an inhibin, and
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14. A method for enhancing survival of at least one neuronal cell having activin receptors responsive to activin, which neuronal cell is provided in a culture of two or more cells in vitro, comprising contacting said cell with an agent, selected from follistatin, proteins that include at least one follistatin module, an α
- 2-macroglobulin, and inhibin, that antagonizes the biological action of activin, in an amount sufficient to enhance survival of said cell.
- View Dependent Claims (15, 16, 17)
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18. A method for inducing at least one progenitor cell to differentiate to a neuronal cell phenotype, which progenitor cell is provided in a culture of two or more cells in vitro, comprising contacting said cell with an agent which disrupts an activin signaling pathway in said cell, wherein
said activin signaling pathway normally induces said cell to differentiate to a non-neuronal cell type, said agent is selected from a soluble growth factor-binding domain of an activin receptor, follistatin, proteins that include at least one follistatin module, an α - 2-macroglobulin, and inhibin, and
said agent is provided in an amount sufficient to induce differentiation of said cell to a neuronal cell phenotype.
- 2-macroglobulin, and inhibin, and
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19. A method for inducing at least one cell having activin receptors responsive to activin to differentiate to a neuronal cell phenotype, which neuronal cell is provided in a culture of two or more cells in vitro, comprising contacting said cell with an agent that antagonizes the biological action of activin, selected from follistatin, proteins that include at least one follistatin module, an α
- 2-macroglobulin, and inhibin, in an amount sufficient to induce neuronal differentiation, wherein said neuronal cell phenotype is selected from a melanocyte progenitor cell, a glial progenitor cell, a sensory neuron progenitor cell, a sympatho-adrenal progenitor cell, a parasympathetic progenitor cell, and an enteric progenitor cell.
- View Dependent Claims (20, 21)
Specification