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US5902741A
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US
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Three-dimensional cartilage cultures
Assignee: Smith and Nephew Inc
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Filing: 1995-06-05
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Granted: 1999-05-11
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Expires: 2015-06-05
Abstract
Abstract The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF- beta in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF- beta . Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope the framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo.
Inventors
- 👤 Anthony F. Purchio
- 👤 Michael Zimber
- 👤 Noushin Dunkelman
- 👤 Gail K. Naughton
- 👤 Brian A. Naughton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 15:55
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/38; A61L27/3886; A61B; A61B90/00; A61K; A61K35/00; A61K35/12; A61K35/28; A61L27/3604; A61L27/3629; A61L27/3637; A61L27/3641; A61L27/3804; A61L27/3839; A61L27/3843; A61L27/3852; A61L27/3895; A61L27/50; A61L27/60; C; C12; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/0652; C12N5/0655; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5008; G01N33/5082; G01N33/5088; A61B10/00; A61B10/02; A61B10/0233; A61B10/025; A61B2010/0258; A61F; A61F2/00; A61F2/0063; A61F2/02; A61F2/04; A61F2/06; A61F2/08; A61K2035/124; A61L2430/00; A61L2430/06; C12N2500/00; C12N2500/30; C12N2500/34; C12N2501/00; C12N2501/10; C12N2501/11; C12N2501/15; C12N2501/30; C12N2501/33; C12N2501/335; C12N2501/38; C12N2501/39; C12N2503/00; C12N2503/04; C12N2510/00; C12N2533/00; C12N2533/30; C12N2533/40; G01N2500/00
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
73 words
A method for preparing a living cartilage tissue in vitro, comprising culturing cartilage-producing stromal cells inoculated onto a three-dimensional framework in a nutrient medium, so that the stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope the framework composed of a biocompatible, non-living material formed into a three dimensional structure having interstitial spaces bridged by the stromal cells to form into a three-dimensional cartilage construct.
Claim 2
Independent Claim
73 words
A method for preparing a living cartilage tissue in vitro, comprising culturing cartilage-producing stromal cells inoculated onto a three-dimensional framework in a nutrient medium, so that the stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope the framework composed of a biocompatible, non-living material formed into a three dimensional structure having interstitial spaces bridged by the stromal cells to form into a three-dimensional cartilage construct.
Claim 3
Dependent Claim
15 words
The method of claim 1 in which the stromal cells are chondrocytes or chondrocyte-progenitor cells.
Claim 4
Dependent Claim
15 words
The method of claim 1 in which the stromal cells are fibroblasts or fibroblast-like cells.
Claim 5
Dependent Claim
22 words
The method of claim 1 in which the stromal cells are umbilical cord cells or bone marrow cells from umbilical cord blood.
Claim 6
Dependent Claim
41 words
The method of claim 1 in which the cells comprise a combination of: chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adipocytes, umbilical cord cells, placental, or bone marrow cells from umbilical cord blood.
Claim 7
Dependent Claim
15 words
The method of claim 1 in which the framework is composed of a biodegradable material.
Claim 8
Dependent Claim
22 words
The method of claim 6 in which the biodegradable material is polyglycolic acid, cotton, cat gut sutures, cellulose, gelatin, collagen or polyhydroxyalkanoates.
Claim 9
Dependent Claim
14 words
The method of claim 1 in which the framework is treated with ethylene oxide.
Claim 10
Dependent Claim
15 words
The method of claim 1 in which the framework is treated with an electron beam.
Claim 11
Dependent Claim
15 words
The method of claim 1 in which the framework is composed of a non-biodegradable material.
Claim 12
Dependent Claim
31 words
The method of claim 10 in which the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene, or a nitrocellulose compound.
Claim 13
Dependent Claim
12 words
The method of claim 1 in which the framework is a mesh.
Claim 14
Dependent Claim
18 words
The method of claim 1 in which the culture medium further comprises of an effective amount of ascorbate.
Claim 15
Dependent Claim
15 words
The method of claim 1 in which the culture medium is kept under static conditions.
Claim 16
Dependent Claim
21 words
The method of claim 1 in which the culture medium is kept in dynamic state by convection and under periodic pressurization.
Claim 17
Dependent Claim
48 words
A living cartilage tissue prepared in vitro, comprising cartilage-producing stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a three-dimensional framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.
Claim 18
Dependent Claim
48 words
A living cartilage tissue prepared in vitro, comprising cartilage-producing stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a three-dimensional framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.
Claim 19
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the stromal cells are chondrocytes or chondrocyte-progenitor cells.
Claim 20
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the stromal cells are fibroblasts or fibroblast-like cells.
Claim 21
Dependent Claim
26 words
The living cartilage tissue of claim 16 in which the stromal cells are umbilical cord cells, placental cells or bone marrow cells from umbilical cord blood.
Claim 22
Dependent Claim
16 words
The living cartilage tissue of claim 16 in which the framework was treated with ethylene oxide.
Claim 23
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the framework was treated with an electron beam.
Claim 24
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the framework is composed of a biodegradable material.
Claim 25
Dependent Claim
24 words
The living cartilage tissue of claim 22 in which the biodegradable material is polyglycolic acid, cotton, cat gut sutures, cellulose, gelatin, collagen or polyhydroxyalkanoates.
Claim 26
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the framework is composed of a non-biodegradable material.
Claim 27
Dependent Claim
33 words
The living cartilage tissue of claim 24 in which the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene, or a nitrocellulose compound.
Claim 28
Dependent Claim
17 words
The living cartilage tissue of claim 16 in which the framework is a mesh or a sponge.
Claim 29
Dependent Claim
37 words
The living cartilage tissue of claim 16 in which the cartilage-producing stromal cells comprise a combination of: chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, muscle cells, umbilical cord cells, placental cells or bone marrow cells from umbilical cord blood.
Claim 30
Dependent Claim
28 words
The method of claim 1, 2, 3, 4 or 5 in which the stromal cells are transfected with an exogenous gene under the control of an expression element.
Claim 31
Dependent Claim
30 words
The living cartilage tissue of claim 16, 17, 18, 19, or 27 in which the stromal cells are transfected with an exogenous gene under the control of an expression element.
Claim 32
Dependent Claim
16 words
The method of claim 2 or 5 in which the chondrocyte-progenitor cells are mesenchymal stem cells.
Claim 33
Dependent Claim
18 words
The living cartilage tissue of claim 19 or 27 in which the chondrocyte-progenitor cells are mesenchymal stem cells.
Claim 34
Dependent Claim
28 words
The method of claim 1 in which the nutrient medium contains a growth factor in an amount effective to enhance the stromal cell production of cartilage matrix proteins.
Claim 35
Dependent Claim
12 words
The method of claim 32 in which the growth factor is TGF-β.
Claim 36
Dependent Claim
18 words
The method of claim 1 in which the stromal cells are cultured on the framework in a bioreactor.
Claim 37
Dependent Claim
24 words
A composition for growing new cartilage comprising mesenchymal stem cells in a polymeric carrier suitable for proliferation and differentiation of the cells into cartilage.
Claim 38
Dependent Claim
24 words
A composition for growing new cartilage comprising mesenchymal stem cells in a polymeric carrier suitable for proliferation and differentiation of the cells into cartilage.
Claim 39
Dependent Claim
16 words
The composition of claim 35 wherein the mesenchymal stem cells are isolated from muscle or dermis.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2002-05-10 | 2002-11-09 | 2003-05-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-05-10 | 2006-11-09 | 2007-05-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-05-10 | 2010-11-09 | 2011-05-11 | $7700.00 | Window Closed / Lapsed |