Neural transplantation using pluripotent neuroepithelial cells

• US 7,048,921 B2
• Filed: 01/12/2001
• Issued: 05/23/2006
• Est. Priority Date: 09/12/1995
• Status: Expired due to Fees

• Current Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Original Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Inventors: Gray, Jeffrey A., Sinden, John, Rashid-Doubell, Fiza, Hodges, Helen, Kershaw, Timothy
• Primary Examiner(s): Wilson, Michael C.
• Application Number:
  US09/760,274
• Publication Number:
  US 20010001662A1
• Time in Patent Office: 1,957 Days
• Field of Search: 424/93.1, 424/93.21, 424/93.2, 435/325
• US Class Current: 424/93.21
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/90 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/24 Interferons [IFN]
• CPC Class Codes: C12N 2501/392 Sexual steroids
• CPC Class Codes: C12N 2501/395 Thyroid hormones
• CPC Class Codes: C12N 2501/91 Heparin
• CPC Class Codes: C12N 5/0623 Stem cells

Abstract

The subject invention pertains to a novel method of correction of behavioral and/or psychological deficits made possible by the intracerebral transplantation of pluripotent neuroepithelial cells. Cells, cell lines, pharmaceutical preparations, medicaments, methods for the production and maintenance of the cell lines for use in the method of the invention are encompassed by the invention.

Claims

1. A method for treating brain damage in a mammal, said method comprising intracerebrally transplanting pluripotent, nestin-positive, neuroepithelial cells into the damaged part of the brain of said mammal, wherein said cells have been genetically modified to be conditionally immortal, wherein said cells are immortal prior to said transplanting and differentiate after said transplanting, and wherein said transplanting improves brain function of said mammal.

2. The method of claim 1, wherein the brain damage is in the hippocampus of said mammal.

3. The method of claim 1, wherein said pluripotent, nestin-positive, neuroepithelial cells are cells of a clonal cell line.

4. The method of claim 1, wherein said method further comprises culturing said pluripotent, nestin-positive, neuroepithelial cells in serum-free medium prior to said transplanting.

5. The method of claim 1, wherein the brain damage is the result of hypoxia.

6. The method of claim 1, wherein said mammal is a human.

7. The method of claim 1, wherein the brain damage causes a cognitive deficit, and wherein said transplanting improves cognitive function of said mammal.

8. The method of claim 1, wherein the genetic modification comprises transduction with a temperature-sensitive oncogene.

9. The method of claim 1, wherein the genetic modification comprises transduction with a temperature-sensitive simian virus 40 large T antigen gene.

10. The method of claim 1, wherein the genetic modification comprises transduction with a temperature-sensitive simian virus 40 large T antigen gene under the control of an interferon-inducible H-2K^b promoter.

11. The method of claim 1, wherein said cells are immortal at 33°

C. and differentiate at 39°

C.

12. A method for treating brain damage in a mammal, said method comprising intracerebrally transplanting human pluripotent, nestin-positive, neuroepithelial cells into the damaged part of the brain of said mammal, wherein said human pluripotent, nestin-positive, neuroepithelial cells comprise a temperature-sensitive simian virus 40 large T antigen gene, and wherein said transplanting improves brain function of said mammal.

13. The method of claim 12, wherein said mammal is human.

14. The method of claim 12, wherein said cells are immortal at 33°

C. and differentiate at 39°

C.

15. The method of claim 12, wherein said temperature-sensitive simian virus 40 large T antigen gene is under the control of an interferon-inducible H-2K^b promoter.

16. A method for treating brain damage in the hippocampus of a mammal, said method comprising intracerebrally transplanting human pluripotent, nestin-positive, neuroepithelial cells into the damaged hippocampus of said mammal, wherein said human pluripotent, nestin-positive, neuroepithelial cells comprise a temperature-sensitive simian virus 40 large T antigen gene, and wherein said transplanting improves cognitive function of said mammal.

17. The method of claim 16, wherein said mammal is human.