Methods and compositions for tissue regeneration

• US 8,679,475 B2
• Filed: 10/24/2012
• Issued: 03/25/2014
• Est. Priority Date: 09/06/2002
• Status: Expired due to Fees

• Current Assignee: Smith & Nephew Incorporated (Smith & Nephew PLC)
• Original Assignee: Smith & Nephew Incorporated (Smith & Nephew PLC)
• Inventors: Rolland, Eric, Hunziker, Thomas, Chevallay, Beatrice, Rinsch, Christopher
• Primary Examiner(s): Gamett, Daniel C
• Application Number:
  US13/659,378
• Publication Number:
  US 20130052168A1
• Time in Patent Office: 517 Days
• Field of Search: None
• US Class Current: 424/93.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/33 Fibroblasts
• 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 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 38/4833 Thrombin (3.4.21.5)
• CPC Class Codes: A61K 41/0023 Agression treatment or altering
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61L 15/40 containing ingredients of undetermined constitution or reaction products thereof , e.g. plant or animal extracts
• CPC Class Codes: A61L 26/0057 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3886 : comprising two or more cell types
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: C12N 2502/094 : keratinocytes
• CPC Class Codes: C12N 2502/1323 : Adult fibroblasts
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2510/04 : Immortalised cells
• CPC Class Codes: C12N 5/0656 : Adult fibroblasts
• CPC Class Codes: C12N 5/0698 : Skin equivalents

Abstract

A kit is disclosed that includes a first component comprising alginate, wherein the first component is comprised in a first sterile vial, and a second component comprising cells comprising keratinocytes or fibroblasts, or mixtures thereof, that secrete one or more biologically active molecules selected from the group consisting of GM-CSF, VEGF, KGF, bFGF, TGFβ, angiopoietin, EGF, IL-Iβ, IL-6, IL-8, TGFα, and TNFα, wherein the cells are allogeneic and mitotically inactive, a buffered solution, and human serum albumin or a cryoprotectant, wherein the second component is comprised in a second sterile vial.

Claims

1. A cell preparation comprising mitotically inactive allogeneic cells that are capable of secreting one or more biologically active molecules selected from the group consisting of GM-CSF, VEGF, KGF, bFGF, TGFβ

, angiopoietin, EGF, IL-1β

, IL-6, IL-8, TGFα

, and TNFα

, wherein the cells are keratinocytes or fibroblasts, or mixtures thereof, and wherein the cell preparation is comprised in a buffered solution, a wound dressing, or an extracellular matrix or matrix material.

2. The cell preparation of claim 1, wherein the cells are mitotically inactivated by irradiation.

3. The cell preparation of claim 1, wherein the cells are differentiated.

4. The cell preparation of claim 1, wherein the concentration of cells are in the range of about 1×

10³ cells/μ

l to about 50×

10³ cells/μ

l.

5. The cell preparation of claim 1, wherein the cells are a mixture of keratinocytes and fibroblasts and the ratio of keratinocytes to fibroblasts is 1:

9.

6. The cell preparation of claim 1, wherein the cell preparation is comprised in a buffered solution.

7. The cell preparation of claim 6, wherein the buffered solution is HBSS.

8. The cell preparation of claim 7, wherein the HBSS comprises Ca⁺⁺ and Mg⁺⁺.

9. The cell preparation of claim 1, wherein the cell preparation is comprised in a wound dressing.

10. The cell preparation of claim 1, wherein the cell preparation is comprised in an extracellular matrix or matrix material.

11. The cell preparation of claim 1, wherein the cell preparation is in the form of a paste.

12. The cell preparation of claim 1, wherein the cell preparation is in the form of a spray.

13. The cell preparation of claim 1, further comprising a cryoprotectant.

14. The cell preparation of claim 13, wherein the cell preparation is cryopreserved.

15. The cell preparation of claim 1, wherein the cell preparation is comprised in a container.

16. The cell preparation of claim 1, wherein the cell preparation is comprised in a sterile vial.

17. A cell preparation comprising mitotically inactive allogeneic cells that are capable of secreting one or more biologically active molecules selected from the group consisting of GM-CSF, VEGF, KGF, bFGF, TGFβ

, angiopoietin, EGF, IL-Iβ

, IL-6, IL-8, TGFα

, and TNFα

, wherein the cells are keratinocytes or fibroblasts, or mixtures thereof, and wherein the cell preparation is in the form of a paste or spray.

18. The cell preparation of claim 17, wherein the cells are mitotically inactivated by irradiation.

19. The cell preparation of claim 17, wherein the cells are differentiated.

20. The cell preparation of claim 17, wherein the concentration of cells are in the range of about 1×

10³ cells/μ

l to about 50×

10³ cells/μ

l.

21. The cell preparation of claim 17, wherein the cells are a mixture of keratinocytes and fibroblasts and the ratio of keratinocytes to fibroblasts is 1:

9.

22. The cell preparation of claim 17, wherein the cell preparation is in the form of a paste.

23. The cell preparation of claim 17, wherein the cell preparation is in the form of a spray.

24. A cell preparation comprising mitotically inactive allogeneic cells that are capable of secreting one or more biologically active molecules selected from the group consisting of GM-CSF, VEGF, KGF, bFGF, TGFβ

, angiopoietin, EGF, IL-Iβ

, IL-6, IL-8, TGFα

, and TNFα

, wherein the cells are a mixture of keratinocytes and fibroblasts and the ratio of keratinocytes to fibroblasts is 1;

9.

25. The cell preparation of claim 24, wherein the cells are mitotically inactivated by irradiation.

26. The cell preparation of claim 24, wherein the cells are differentiated.

27. The cell preparation of claim 24, wherein the concentration of cells are in the range of about 1×

10³ cells/μ

l to about 50×

10³ cells/μ

l.

28. The cell preparation of claim 24, wherein the cell preparation is comprised within a biologically acceptable carrier.

29. A cell preparation comprising mitotically inactive allogeneic cells that are capable of secreting one or more biologically active molecules selected from the group consisting of GM-CSF, VEGF, KGF, bFGF, TGFβ

, angiopoietin, EGF, IL-Iβ

, IL-6, IL-8, TGFα

, and TNFα

, wherein the cells are keratinocytes or fibroblasts, or mixtures thereof, and wherein the cell preparation further comprises a cryoprotectant.

30. The cell preparation of claim 29, wherein the cells are mitotically inactivated by irradiation.

31. The cell preparation of claim 29, wherein the cells are differentiated.

32. The cell preparation of claim 29, wherein the concentration of cells are in the range of about 1×

10³ cells/μ

l to about 50×

10³ cells/μ

l.

33. The cell preparation of claim 29, wherein the cell preparation is cryopreserved.

34. The cell preparation of claim 29, wherein the cell preparation is comprised within a biologically acceptable carrier.