Functional myelination of neurons

Patent metadata

Field	Value
Publication number	US-10920194-B2
Application number	US-201715802845-A
Country	US
Kind code	B2
Filing date	Nov 3, 2017
Priority date	Aug 28, 2014
Publication date	Feb 16, 2021
Grant date	Feb 16, 2021

Abstract

Hair follicle bulge region/LLP region CD34(+) MeSCs can be isolated from mammalian skin bearing hair follicles. These cells are multipotent and retain the ability to differentiate into cells of neural crest lineage, including glia-like cells that express the glial marker Gfap, and are able to express myelin basic protein, and to remyelinate naked (unmyelinated or demyelinated) neuronal processes with a functional, dense myelin sheath. These cells of neural crest lineage can be used to produce a dense myelin sheath on neurons which lack myelin due to genetic defect, trauma, toxin, infection, or disease process. Therefore, embodiments of the invention provide methods for preparing such cells, the cells themselves and compositions containing the cells, as well as methods for using the cells.

First claim

What is claimed is:

1. A method of producing a functional myelin sheath on one or more neurites of neurons that lack a functional myelin sheath, comprising contacting the neurons with isolated myelin-depositing cells which:
(a) are CD34(+) melanocyte stem cells from the bulge region, the lower permanent portion, or both, of the hair follicle of a mammal that have been exposed to neural crest differentiation medium also containing 10 μM ascorbic acid;
(b) have no visible pigmentation;
(c) express glial fibrillary acid protein, and Tuj1 (β3-tubulin); and
(d) express myelin basic protein and produce a functional multilayered myelin sheath surrounding the neurites of unmyelinated neurons when contacted with the unmyelinated neurites,
wherein contacting is achieved by co-culturing the CD34(+) multipotent neural crest progenitor cells and neurons that lack a functional myelin sheath together in poly-D-lysine and laminin-coated vessels in neural crest differentiation medium including 10 μM ascorbic acid.

2. A method of producing a functional myelin sheath on one or more neurites of neurons that lack a functional myelin sheath, comprising contacting the neurons with isolated myelin-depositing cells which:
(a) are CD34(+) melanocyte stem cells from the bulge region, the lower permanent portion, or both, of the hair follicle of a mammal that have been exposed to neural crest differentiation medium also containing 10 μM ascorbic acid;
(b) have no visible pigmentation;
(c) express glial fibrillary acid protein, and Tuj1 (β3-tubulin); and
(d) express myelin basic protein and produce a functional multilayered myelin sheath surrounding the neurites of unmyelinated neurons when contacted with the unmyelinated neurites,
wherein contacting is achieved by direct injection, intrathecal injection, intravenous injection, or stereotaxic injection of the CD34(+) multipotent neural crest progenitor cells into a subject having neurons that lack a functional myelin sheath.

3. The method of claim 2 wherein the neurons that lack a functional myelin sheath are in the-peripheral nervous system of the subject.

4. The method of claim 2 wherein the neurons that lack a functional myelin sheath are in the-central nervous system of the subject.

5. The method of claim 2 wherein the subject suffers from demyelination.

6. The method of claim 5 wherein the demyelination is caused by trauma, a toxin, a bacterial infection, a viral infection, a parasitic infection, an autoimmune disease or a demyelinating disease.

7. The method of claim 6 wherein the demyelinating disease is selected from the group consisting of experimental allergic encephalomyelitis, acute disseminated encephalomyelopathy, acute hemorrhagic encephalomyelopathy, experimental allergic neuritis, amoebic meningoencephalitis, Guillain-Barre syndrome, multiple sclerosis, stroke, traumatic brain injury, traumatic peripheral nerve injury, Devic's disease (otherwise known as neuromyelitis optica (NMO)), NMO spectrum disorder, progressive multifocal leukoencephalopathy, central pontine myelinolysis, Tabes dorsalis , optic neuritis, transverse myelitis, progressive inflammatory neuropathy, myelopathy, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, and visna.

Assignees

• The Univ Of Maryland Baltimore
• Us Veterans Affairs
• Univ Maryland

Inventors

• Hornyak Thomas
• Joshi Sandeep

Classifications

• A61K35/36 Primary

  Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39) · CPC title

• C12N2506/091

  from melanocytes · CPC title

• C12N5/0626

  Melanocytes · CPC title

• C12N2501/365

  Endothelin · CPC title

• C12N2501/33

  Insulin · CPC title