Augmentation and repair of spincter defects with cells including fibroblasts

• US 20080112935A1
• Filed: 10/31/2007
• Published: 05/15/2008
• Est. Priority Date: 11/05/1999
• Status: Abandoned Application

• Current Assignee: Adriana Soto, Donald Kleinsek
• Original Assignee: Adriana Soto, Donald Kleinsek
• Inventors: Soto, Adriana, Kleinsek, Donald
• Application Number:
  US11/981,852
• Publication Number:
  US 20080112935A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• 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 35/12 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: A61K 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/1858 Platelet-derived growth factor [PDGF]
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• 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 27/3873 Muscle tissue, e.g. sphincter
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 5/066 Tenocytes; Tendons, Ligaments

Abstract

An embodiment of the invention includes methods for the long-term augmentation and/or repair of skin defects (scars, skin laxness, skin thinning, and skin augmentation), cellulite, breast tissue, wounds and burns, urological and gastroesophageal sphincter structures, hernias, periodontal disease and disorders, tendon and ligament tears and baldness, by the injection or direct surgical placement/implantation of autologous cultured cells and/or cultured cell-produced extracellular matrix that is derived from connective tissue, dermis, fascia, lamina propria, stroma, adipose tissue, muscle, tendon, ligament or the hair follicle. The corrective application is done on tissue proximal or within the area of the defect. The method involves retrieving viable cells from the subject, a neonate or human fetus. Alternatively, the corrective application involves the cells placed in a matrix, preferably comprised of autologous extracellular matrix constituents as a three-dimensional structure or as a suspension, prior to placement into a position with respect to the subject'"'"'s defect. In a further embodiment, the preferable autologous extracellular matrix constituents are collected from culture and placed in a position with respect to the subject'"'"'s defect.

Claims

1. A method for repair or augmentation of a tissue defect in a subject, comprising choosing a sphincter structure malfunction as the defect, and placing within or proximal to the tissue defect site a composition comprising an enriched population of in vitro cultured mammalian fibroblasts to repair or augment the sphincter structure malfunction.

2. The method of claim 1, wherein the fibroblast cells are autologous to the subject.

3. The method of claim 1 wherein the subject is a human.

4. The method of claim 1, comprising retrieving cells from a tissue chosen from at least one member of the group consisting of dermis, fascia, adipose tissue, lamina propria, stroma, connective tissue, tendon, ligament, muscle, hair follicle region, and dermal papilla for the culture of the cultured mammalian fibroblasts.

5. The method of claim 1, wherein the fibroblasts comprise dermal, papillary, reticular, fascial, lamina propria, dermal papilla, stromal, or connective tissue fibroblasts.

6. The method of claim 1, wherein the composition is placed into the tissue by a method selected from the group consisting of injection, engraftment, engraftment by threading, and direct placement.

7. The method of claim 1, wherein the composition is placed in connective tissue of a sphincter, the muscle tissue of a sphincter, or a combination thereof.

8. The method of claim 1, wherein the sphincter structure malfunction results in, or is caused by a condition of, incontinence, urinary incontinence, vesicoureteral incontinence, or gastroesophageal reflux.

9. The method of claim 1, wherein the sphincter structure malfunction results in, or is caused by stress urinary incontinence, female urinary incontinence, mixed urinary incontinence, overflow incontinence, or urge incontinence.

10. The method of claim 1, wherein the fibroblast cells are taken from a cells derived from tissue sources protected from light and chemical exposure, from a fetus, or from a juvenile.

11. The method of claim 1, wherein the composition further comprises at least one member of the group consisting of myofibroblasts, adipocytes and/or preadipocytes, muscle cells, smooth muscle cells, skeletal muscle cells, striated muscle cells, myoblasts, nondifferentiated mesenchymal cells, and other cell types.

12. The method of claim 11 wherein the cells are autologous.

13. The method of claim 1, further comprising enzymatically digesting a tissue sample to obtain mammalian cells for starting the mammalian cell culture.

14. The method of claim 1, wherein the cultured mammalian cells are harvested by enzymatic or non-enzymatic means in vitro for the placement within or proximal to the defect.

15. The method of claim 1, further comprising of at least one step chosen from the group consisting of collecting cell-produced extracellular matrix enzymatically, mechanically or chemically from the culture for inclusion in the composition, storing the in vitro cultured mammalian cells prior to introduction into the treatment site, and freezing the in vitro cultured cells prior to introduction into the treatment site.

16. The method of claim 1, further comprising culturing the mammalian cells in vitro in the presence of at least one member of the group consisting of fibronectin, collagen, crosslinked collagen, human collagen, bovine collagen, porcine collagen, glycosaminoglycans, hyaluronic acid, ground substance, proteoglycan, fibrillin, laminin, elastin, fibrin, and fibrinogen.

17. The method of claim 1, further comprising culturing the cultured mammalian cells in vitro with autologous serum, human serum, nonhuman serum, or serum-free medium.

18. The method of claim 1, wherein the cells are passaged during in vitro culture.

19. The method of claim 1, wherein the composition further comprises serum.

20. The method of claim 1, wherein the composition placed into the tissue further comprises extracellular matrix isolated from extracellular matrix materials produced by cells from the in vitro culture of the cells.

21. The method of claim 1, wherein the composition further comprises, prior to combination with cells, at least one member of the group consisting of fibronectin, collagen, crosslinked collagen, human collagen, bovine collagen, porcine collagen, glycosaminoglycans, hyaluronic acid, ground substance, proteoglycan, fibrillin, laminin, elastin, fibrin, fibrinogen and other similar extracellular matrix.

22. The method of claim 1, wherein the composition further comprises at least one member of the exogenous tissue growth factor group consisting of PDGF, TGF-beta, FGF, EGF, IGF-I and IGF-II.

23. The method of claim 1, wherein the composition further comprises at least one member of the group consisting of non-degradable and biologic-tolerant synthetic prosthesis materials, cellular mesh, dextranomer microspheres, polylactic acids, prosthetic mesh, prosthetic plug, cellulose, granules, sheets, creams, foam, pectin, cloth, biodegradable microspheres, hydrogel, hydrocolloid, gauze, polyurethane, charcoal, hydrophobic foam, hydrophilic foam, starch, absorptive powders, pastes, nylon meshes, solid polymer particles, polypropylene mesh, and polyester mesh.

24. The method of claim 1, wherein the composition further comprises at least one member of the group consisting of gelatin, hydroxyapatite, polyglycolic acid, acellular mesh, biodegradable materials, biodegradable polymer, alginate, cordal granules, gel, colloidal particles, hydroactives, polymer, suture, copolymer films, and biocompatible fillers.

25. A composition for repairing or augmenting a sphincter malfunction defect proximal or within the defect, the composition comprising in vitro cultured mammalian fibroblasts.