OLIGODENDROCYTES DERIVED FROM HUMAN EMBRYONIC STEM CELLS FOR REMYELINATION AND TREATMENT OF SPINAL CORD INJURY

• US 20090232779A1
• Filed: 01/21/2009
• Published: 09/17/2009
• Est. Priority Date: 07/11/2002
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Keirstead, Hans S., Nistor, Gabriel I.
• Granted Patent: US 10,611,998 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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: 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/395 Thyroid hormones
• CPC Class Codes: C12N 2503/02 Drug screening
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 5/0606 Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0622 Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
• CPC Class Codes: C12N 5/0623 Stem cells

Abstract

This invention provides populations of neural cells bearing markers of glial cells, such as oligodendrocytes and their precursors. The populations are generated by differentiating pluripotent stem cells such as human embryonic stem cells under conditions that promote enrichment of cells with the desired phenotype or functional capability. Various combinations of differentiation factors and mitogens can be used to produce cell populations bearing markers of oligodendrocyte precursor cells. Upon further differentiation form complex processes characteristic of mature oligodendrocytes. The cells are capable of forming myelin sheaths, and can be used therapeutically improve function of the central nervous system.

Claims

1. (canceled)

2. A system for generating glial cells, comprising a line of undifferentiated pPS cells;

and a differentiated cell population in which at least 80% of the cells have the following characteristics;

they are the in vitro progeny of the primate pluripotent stem (pPS) cell line;

they stain with antibody specific for NG2 proteoglycan; and

they are negative for the neuronal marker NeuN.

3. The system of claim 2, wherein at least 80% of the cells in the differentiated cell population also express A2B5.

4. The system of claim 2, wherein at least 80% of the cells in the differentiated cell population also express platelet-derived growth factor receptor-α

(PDGFRα

).

5. The system of claim 2, wherein at least 20% of the cells in the differentiated cell population show a bipolar morphology characteristic of oligodendrocyte precursors.

6. The system of claim 2, at least 10% of the cells in the differentiated cell population have complex processes characteristic of mature oligodendrocytes.

7. The system of claim 2, wherein implantation of the differentiated cell population into the spinal cord of a shiverer mutant mouse causes deposition of compact myelin around neuronal axons.

8. The system of claim 2, wherein implantation of the differentiated cell population in or around the spinal cord in a contusion-injured rat causes improvement in overground locomotion compared with a contusion injured rat that does not receive the implantation of the differentiated cell population.

14. The system of claim 2, wherein the pPS cells are human embryonic stem (hES) cells.

26. A pharmaceutical composition, comprising the differentiated cell population according to claim 2.

35. The system of claim 2, wherein the pPS cell line is comprised of cells expressing stage specific embryonic antigen 3 (SSEA3), stage specific embryonic antigen 4 (SSEA4) and markers detectable using antibodies designated Tra-1-60 and Tra-1-81.

9-13. -13. (canceled)

15-25. -25. (canceled)

27-34. -34. (canceled)