Bone-marrow derived neurogenic cells and uses thereof
First Claim
4. The neurogenic cell of claim 1-3, further comprising an expression vector comprising a nucleic acid sequence encoding a therapeutic or reporter gene.
2 Assignments
0 Petitions
Accused Products
Abstract
Disclosed are cellular compositions, grafts and pharmaceutical products made from bone marrow (BM) cells useful for a wide array of cell-based therapies for diseases and disorders of the nervous system. Transgenic cells in accord with the invention express therapeutic or reporter genes encoded in viral vectors. The cells are capable of extensive expansion in vitro and can generate neurons and glial cells both in culture and in vivo. Upon administration to a nervous system tissue or site in a host subject, the cells can migrate to appropriate target sites and can assimilate therein, differentiating into both neurons and astrocytes without evidence of fusion with endogenous cells of the host nervous tissue. The cells can express an array of therapeutic gene products suitable for treatment of nervous system disorders. Particularly preferred for neurodegenerative disease applications are transgenic BM-derived neurogenic cells expressing neurotrophic factors.
-
Citations
23 Claims
-
4. The neurogenic cell of claim 1-3, further comprising an expression vector comprising a nucleic acid sequence encoding a therapeutic or reporter gene.
- 5. An isolated population of neurogenic cells derived from bone marrow comprising cells capable of differentiating into a neuron or glial cell in vitro or when administered to a host subject.
-
14. A method for delivering a bone-marrow derived neurogenic cell to a neural tissue of a host subject, comprising:
-
(a) culturing a population of bone marrow-derived cells under conditions to obtain an isolated neurogenic cell from the cell population; (b) expanding said neurogenic cell in vitro, to obtain a cell population or graft enriched in bone marrow-derived neurogenic cells; and (c) administering the cell population or graft of step (b) into the host subject, wherein a bone marrow-derived neurogenic cell or a progeny cell derived from said neurogenic cell populates at least one neural tissue of the subject. - View Dependent Claims (1, 2, 3, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 22, 23)
-
-
17-1. The method of claim 14, wherein the administered neurogenic cell populates the brain of the subject.
-
18-2. The method of claim 14, wherein the administered neurogenic cell populates the spinal cord of the subject.
-
19-3. The method of claim 14, wherein the administered neurogenic cell populates a component of the peripheral nervous system of the subject.
-
20. The method of claim 14, wherein the neurogenic cell of step (b) comprises the following marker expression profile in vitro:
-
undetectable or low levels of at least one of CD34, CD45, and CD11b; detectable levels of at least one of CD105 and CD109; undetectable or low levels of c-kit and detectable levels of sca-1; and detectable or high levels of at least one of nestin, β
-III tubulin, and NFM,and optionally, detectable levels of GFAP, as determined by standard marker detection assay. - View Dependent Claims (21)
-
-
20-4. A method for expressing a therapeutic or reporter gene in a neural tissue, comprising:
-
(a) culturing a population of bone marrow-derived cells under conditions to obtain an isolated neurogenic cell from the cell population; (b) expanding said neurogenic cell in vitro, to obtain a cell population or graft enriched in bone marrow-derived neurogenic cells; (c) contacting the neurogenic cell of step (a) or (b) with an expression vector comprising a therapeutic or reporter gene, to obtain transgenic bone marrow-derived neurogenic cells transduced with said vector; and (d) administering the cell population or graft of step (c) into the host subject, wherein a transgenic neurogenic cell or a progeny cell derived therefrom populates at least one neural tissue of the subject and expresses the therapeutic or reporter gene.
-
Specification