Compositions and methods for treating bone, joints and cartilage

• US 10,500,233 B2
• Filed: 02/12/2015
• Issued: 12/10/2019
• Est. Priority Date: 02/12/2014
• Status: Active Grant

• Current Assignee: RepliCel Life Sciences, Inc.
• Original Assignee: RepliCel Life Sciences, Inc.
• Inventors: Hoffmann, Rolf, McElwee, Kevin John
• Primary Examiner(s): Davis, Ruth A
• Application Number:
  US15/118,391
• Publication Number:
  US 20170173084A1
• Time in Patent Office: 1,762 Days
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/36 Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells islets of Langerhans A61K35/39
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C12N 5/0627 Hair cells

Abstract

Briefly stated, the present invention provides compositions and methods for treating or preventing joint injuries utilizing hair follicle derived Non-Bulbar Dermal Sheath (“NDBS”) cells. Within one aspect of the invention methods are provided for isolating NBDS cells, comprising the steps of: (a) preparing vital hair; (b) cleaving the hair prepared in step (a) to remove the hair follicle bulb; (c) isolating Non-Bulbar Dermal Sheath tissue; and (d) cultivating the isolated Non-Bulbar Dermal sheath tissue to produce NBDS cells. Within one embodiment of the invention the vital hair is obtained by full skin biopsy from the occipital scalp of a subject.

Claims

1. A method for treating a joint, comprising the step of administering into a joint of a subject a composition comprising isolated Non-Bulbar Dermal Sheath (NBDS) cells, where the NBDS cells have been isolated from an outer dermal sheath of a hair follicle, where the outer dermal sheath of the hair follicle is located above the bulbar portion of the hair root but below the base of the sebaceous gland canal.

2. The method according to claim 1 wherein said treatment is due to a joint injury.

3. The method according to claim 2 wherein said joint injury is an acute or chronic osteoarthrosis.

4. The method according to claim 1 wherein said isolated NBDS cells are provided by a method comprising:

(a) obtaining vital hair from a subject;

(b) cleaving the hair obtained in step (a) to remove the hair follicle bulb and obtain an isolated dermal sheath;

(c) isolating Non-Bulbar Dermal Sheath tissue from the dermal sheath product of step (b); and

(d) cultivating the isolated Non-Bulbar Dermal sheath tissue to produce isolated NBDS cells.

5. The method according to claim 4 wherein said vital hair is obtained by biopsy from a hair on the scalp of a subject.

6. The method according to claim 4 wherein said isolated NBDS cells can either be used autologous or allogenic.

7. The method according to claim 4 wherein said hair is cleaved utilizing a micromanipulator and scalpel, or scissors.

8. The method according to claim 4, further comprising the step of digesting said isolated Non-Bulbar Dermal Sheath tissue by an enzymatic digestion.

9. The method according to claim 8 wherein said enzymatic digestion comprises an enzyme selected from the group consisting of collagenase hyaluronidase, DNAse, elastase, papain, protease type XIV, trypsin, and dispase.

10. The method according to claim 4 wherein said NBDS cells are passaged over multiple passages.

11. The method of claim 1 wherein said composition further comprises serum plasma or platelet-rich plasma (PRP).

12. The method of claim 1 wherein said composition further comprises fibrin and/or hyaluronic acid.

13. The method of claim 1 wherein said composition further comprises at least one of (a) a component of the extracellular matrix, (b) a cytokine, (c) a chemokine or (d) a therapeutic agent.

14. The method of claim 13 wherein said composition comprises one or more components selected from the group consisting of glycosaminoglycans (GAGS), heparin sulfate, chondroitin sulfate, keratin sulfate, hyaluronic acid, elastin, collagens, fibronectins and laminins.

15. The method of claim 13 wherein said composition comprises one or more cytokines selected from the group consisting of transforming growth factor beta (TGF-beta), insulin-like growth factor (IGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), parathyroid-hormone-related protein, hepatocyte growth factor/scatter factor (HGF/SF), macrophage stimulating protein (MSP), epidermal growth factor (EGF), interleukin 6 (IL-6), stromal cell-derived factor 1 (SDF-1), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF).

16. The method of claim 13 wherein said composition comprises one or more therapeutic agents selected from the group consisting of analgesic agent, anti-inflammatory agent, antibiotic, antiviral, antimitotic, and immunomodulatory agent.

17. The method of claim 1 wherein said composition further comprises a scaffold.

18. The method of claim 17 wherein said scaffold is a biodegradable scaffold.

19. The method of claim 1 wherein said composition further comprises NBDS cell culture supernatant.

20. The method of claim 1 wherein said composition does not contain bulbar cells.