Methods of generating glial and neuronal cells and use of same for the treatment of medical conditions of the CNS

Patent metadata

Field	Value
Publication number	US-9631175-B2
Application number	US-201414329510-A
Country	US
Kind code	B2
Filing date	Jul 11, 2014
Priority date	Aug 28, 2006
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

A method of generating neural and glial cells is provided. The method comprising growing human stem cells under conditions which induce differentiation of said human stem cells into the neural and glial cells, said conditions comprising the presence of retinoic acid and an agent capable of down-regulating Bone Morphogenic Protein activity.

First claim

What is claimed is:

1. A method of enhancing myelination in the CNS of a subject, the method comprising directly administering at a site within the CNS of a subject in need thereof a therapeutically effective amount of an isolated oligodendrocyte or astrocyte, thereby enhancing myelination at the site of administration, wherein the isolated oligodendrocyte or astrocyte is generated by:
(a) culturing in suspension human embryonic stem cells in the presence of retinoic acid and epidermal growth factor (EGF) to generate neurospheres;
(b) contacting said neurospheres with EGF and bFGF on an adherent substrate, wherein said adherent substrate comprises an extracellular matrix component; and
(c) contacting said neurospheres following step (b), wherein said neurospheres are intact or dissociated, with a medium comprising noggin, said medium being devoid of EGF and bFGF, thereby generating the oligodendrocyte or astrocyte.

2. The method of claim 1 , wherein the subject suffers from a medical condition selected from the group consisting of autoimmune diseases, Guillan-Barre syndrome or congenital leukodystrophies, adrenoleukodystrophies, Pelizaeus-Merzbacher, Charcot-Marie-Tooth, Krabbe or Alexander disease, vanishing white matter syndrome, progressive multifocal leukoencephalopathy, infectious demyelinating diseases, postinflammatory demyelinated lesions, neurodegenerative diseases, multisystem degeneration, vascular diseases, ischemic white matter damage, vascular leukoencephalopathies, subcortical infarcts, brain trauma, spinal cord trauma, demyelinative injury, neoplasms and oligodendrio-glioma.

3. The method of claim 1 , wherein said cells comprise oligodendrocytes and the subject suffers from insufficient myelination.

4. The method of claim 1 , wherein said cells comprise astrocytes and the subject suffers from a medical condition selected from the group consisting of Alexander disease, epilepsy, Alzheimer's disease, spinal cord injury, traumatic brain injury and neurogenesis deficiencies.

Assignees

• Yeda Res & Dev
• Yeda Res And Dev Co Ltd At The Weizmann Inst Of Science

Inventors

• Revel Michel
• Chebath Judith
• Izrael Michal
• Kaufman Rosalia

Classifications

• C12N2506/02

  from embryonic cells · CPC title

• C12N2533/90

  Substrates of biological origin, e.g. extracellular matrix, decellularised tissue · CPC title

• C12N2501/385

  of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR] · CPC title

• A61K35/30 Primary

  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 title

• C12N2501/11

  Epidermal growth factor [EGF] · CPC title