Use of adipose tissue-derived stromal cells for chondrocyte differentiation and cartilage repair

• US 8,048,673 B2
• Filed: 04/21/2006
• Issued: 11/01/2011
• Est. Priority Date: 08/19/1999
• Status: Expired due to Fees

• Current Assignee: Cognate BioServices, Inc.
• Original Assignee: Artecel Sciences Inc.
• Inventors: Halvorsen, Yuan-Di C., Wilkison, William O., Gimble, Jeffrey M.
• Primary Examiner(s): Kim; Taeyoon
• Application Number:
  US11/408,381
• Publication Number:
  US 20060188985A1
• Time in Patent Office: 2,020 Days
• Field of Search: 435/325, 435/366, 435/377, 435/395, 435/455, 424/93.21, 424/93.7
• US Class Current: 435/377
• 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: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• 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 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C12N 2500/30 Organic components
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/98 Xeno-free medium and culture conditions
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2501/999 Small molecules not provided for elsewhere
• CPC Class Codes: C12N 2502/1305 Adipocytes
• CPC Class Codes: C12N 2506/1384 from adipose-derived stem cells [ADSC], from adipose stromal stem cells
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 5/0653 Adipocytes; Adipose tissue
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

Methods and compositions for directing adipose-derived stromal cells cultivated in vitro to differentiate into cells of the chondrocyte lineage are disclosed. The invention further provides a variety of chondroinductive agents which can be used singly or in combination with other nutrient components to induce chondrogenesis in adipose-derived stromal cells either in cultivating monolayers or in a biocompatible lattice or matrix in a three-dimensional configuration. Use of the differentiated chondrocytes for the therapeutic treatment of a number of human conditions and diseases including repair of cartilage in vivo is disclosed.

Claims

1. A method of treating a cartilage defect in a mammal, the method comprising:

a) producing a synthetic cartilage patch, wherein said synthetic cartilage patch comprises an isolated adipose tissue derived stromal cell that has been differentiated in vitro to express at least one characteristic of a chondrocyte; and

b) surgically implanting said synthetic cartilage patch to a cartilage defect area in said mammal.

2. The method of claim 1, wherein the cartilage patch is grown in pre-shaped culture wells to produce a patch of specific dimensions.

3. The method of claim 1, wherein the cartilage patch is grown in culture wells coated with a molecule that discourages adhesion of chondrogenic cells to the cell contacting surface.

4. The method of claim 3, wherein the culture wells have a cross-sectional surface area of about 25 cm².

5. The method of claim 3, wherein the culture wells have a depth large enough to form a cartilage patch of about 0.3 cm.

6. The method of claim 3, wherein the coating molecule is selected from the group consisting of dichlorodimethylsilane and polytetrafluoroethylene based reagents.

7. The method of claim 3, wherein the culture wells are cast from a pliable or moldable biocompatible material that does not permit the attachment of the adipose tissue derived stromal cell that has been differentiated in vitro to express at least one characteristic of a chondrocyte.

8. The method of claim 7, wherein the pliable or moldable biocompatible material is selected from the group consisting of agarose, glass, untreated cell culture plastic, and polytetrafluoroethylene.