The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Mediators of hedgehog signaling pathways, compositions and uses related thereto

Cells derived from human umbilical cords are disclosed along with methods for their therapeutic use. Isolation techniques, culture methods and detailed characterization of the cells with respect to their cell surface markers, gene expression, and their secretion of trophic factors are described.

Postpartum cells derived from umbilical cord tissue, and methods of making and using the same

The present invention reveals an in vitro procedure by which a homogeneous population of multipotential precursor cells from mammalian embryonic neuroepithelium (CNS stem cells) can be expanded up to 10 9 fold in culture while maintaining their multipotential capacity to differentiate into neurons, oligodendrocytes, and astrocytes. Chemically defined conditions are presented that enable a large number of neurons, up to 50% of the expanded cells, to be derived from the stem cells. In addition, four factors--PDGF, CNTF, LIF, and T3--have been identified which, individually, generate significantly higher proportions of neurons, astrocytes, or oligodendrocytes. These defined procedures permit a large-scale preparation of the mammalian CNS stem cells, neurons, astrocytes, and oligodendrocytes under chemically defined conditions with efficiency and control. These cells should be an important tool for many cell- and gene-based therapies for neurological disorders.

Isolation propagation and directed differentiation of stem cells from embryonic and adult central nervous system of mammals

The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in Figures 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Small organic molecule regulators of cell proliferation

Isolation, characterization, proliferation, differentiation and transplantation of mammalian neural stem cells is disclosed.

Human CNS neural stem cells

The invention provides methods of transplanting multipotent neural stem cell progeny to a host by obtaining a population of cells derived from mammalian neural tissue containing at least one multipotent CNS multipotent neural stem cell; culturing the neural stem cell in a culture medium containing one or more growth factors which induce multipotent neural stem cell proliferation; inducing proliferation of the multipotent neural stem cell to produce neural stem cell progeny which includes multipotent neural stem cell progeny cells; and transplanting the multipotent neural stem cell progeny to the host. Also provided are methods of transplanting neural stem cell progeny to a host by obtaining an in vitro cell culture containing CNS neural stem cells where one or more cells in the culture (i) proliferates in a culture medium supplemented with one or more mitrogens, (ii) retains the capacity for renewed proliferation, and (iii) maintains the multipotential capacity, under suitable culture conditions, to differentiate into neurons, astrocytes, and oligodendrocytes; and transplanting the one or more cells to the hose.

Neural transplantation using proliferated multipotent neural stem cells and their progeny

Methods are described for increasing the number of neural stem cells that differentiate into astrocytes, oligodendrocytes, or neurons. The methods comprise proliferating isolated neural stem cells in a culture medium having a first growth factor to produce precursor cells. The precursor cells are then differentiated into astrocytes, oligodendrocytes, or neurons in a second culture medium, free of the first growth factor, containing a second growth factor or combination of growth factors.

Biological factors and neural stem cells

A method for the remyelination of neurons is disclosed wherein neural stem cells isolated from adult or fetal neural tissue are proliferated in a culture medium containing a growth factor to produce precursor cells having a nestin (+) phenotype. The precursor cells are capable of differentiation into oligodendrocytes which, when associated with a demyelinated neuron, effect remyelination.

Remyelination using neural stem cells

Genetically modified, epidermal growth factor-responsive neural stem cells are disclosed that are capable of differentiating into neurons, astrocytes, and oligodendrocytes in vitro. The stem cells can be proliferated in vitro to result in large numbers of cells for use in transplantation to treat various neurological disorders. The stem cells can be obtained from a human or other animal, cultured in vitro in the presence of a growth factor and genetically modified with desired DNA using techniques known in the art. Alternatively, the precursor cells can be derived from a transgenic animal which has had a desired gene inserted into its genome.

Genetic modification of neural stem cells.

Endogenous precursor cells are manipulated/modified in situ to induce the cells, by the application of one or more growth factors or similar compounds, to proliferate, differentiate and migrate within the CNS so as to replace lost or non-functional cells. The precursor cells are also altered in situ (in vivo) so as to secrete a compound which alters the function of other differentiated CNS cells. The endogenous precursor cells can also be treated with one or more growth factors in situ in order to increase the yield of stem cells that can be isolated from the adult CNS and proliferated in vitro.

Weiss Samuel

Papers

Neural transplantation using proliferated multipotent neural stem cells and their progeny

Biological factors and neural stem cells

Remyelination using neural stem cells

Genetic modification of neural stem cells.

In situ modification and manipulation of stem cells of the central nervous system