Regeneration and augmentation of bone using mesenchymal stem cells

• US 6,541,024 B1
• Filed: 03/13/1998
• Issued: 04/01/2003
• Est. Priority Date: 04/19/1996
• Status: Expired due to Term

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: Kadiyala, Sudhakar, Bruder, Scott P.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/042,275
• Time in Patent Office: 1,845 Days
• Field of Search: 424/426, 523/114, 523/115, 623/16
• US Class Current: 424/426
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/222 Gelatin
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C08L 1/02 Cellulose; Modified cellulose
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/42 Organic phosphate, e.g. beta glycerophosphate
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/18 : Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 2533/52 : Fibronectin; Laminin
• CPC Class Codes: C12N 2533/54 : Collagen; Gelatin
• CPC Class Codes: C12N 5/0654 : Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

Disclosed are compositions and methods for augmenting bone formation by administering isolated human mesenchymal stem cells (hMSCs) with a ceramic material or matrix or by administering hMSCs; fresh, whole marrow; or combinations thereof in a resorbable biopolymer which supports their differentiation into the osteogenic lineage. Contemplated is the delivery of (i) isolated, culture-expanded, human mesenchymal stem cells; (ii) freshly aspirated bone marrow; or (iii) their combination in a carrier material or matrix.

Claims

1. A method of augmenting bone formation in an individual in need thereof by administering to said individual isolated human mesenchymal stem cells with a resorbable biopolymer selected from the group consisting of a gelatin, collagen, and cellulose, wherein said resorbable biopolymer supports the differentiation of such stem cells into the osteogenic lineage to an extent sufficient to generate bone formation therefrom.

5. The method of claim 1 wherein the medium is a powder, sponge, strip, film, gel or web or a structurally stable, three dimensional implant in the form of a cube, cylinder or block or in the shape of an anatomical form.

6. The method of claim 1 wherein the resorbable biopolymer is a porcine skin-derived gelatin.

7. The method of claim 1 which further comprises administering to said individual at least one bioactive factor which induces or accelerates the differentiation of such mesenchymal stem cells into the osteogenic lineage.

8. The method of claim 7 wherein the cells are contacted with the bioactive factor ex vivo.

9. The method of claim 8 wherein the cells are contacted with the bioactive factor when in contact with the matrix which supports the differentiation of such stem cells into the osteogenic lineage to an extent sufficient to generate bone formation therefrom.

10. The method of claim 7 wherein the bioactive factor is a synthetic glucocorticoid.

11. The method of claim 10 wherein the synthetic glucocorticoid is dexamethasone.

12. The method of claim 7 wherein the bioactive factor is a bone morphogenic protein.

13. The method of claim 12 wherein the bone morphogenic protein is in a liquid or semi-solid carrier suitable for intramuscular, intravenous, intramedullary or intra-articular injection.

14. The method of claim 12 wherein the bone morphogenic protein is selected from the group consisting of BMP-2, BMP-3, BMP4, BMP-6 and BMP-7.

2. A composition for augmenting bone formation, said composition comprising a resorbable biopolymer selected from the group consisting of gelatin, cellulose, and collagen, in combination with isolated mesenchymal stem cells.

15. A method for augmenting bone formation in an individual in need thereof which comprises administering to said individual thereof a bone formation augmenting amount of the composition of claim 2.

3. A composition for augmenting bone formation, said composition comprising a resorbable biopolymer selected from the group consisting of gelatin, cellulose, and collagen, wherein said resorbable biopolymer is a sponge, strip, film, gel, or web, or a structurally stable, three dimensional implant, in combination with isolated mesenchymal stem cells.

16. A method for augmenting bone formation in an individual in need thereof which comprises administering to said individual thereof a bone formation augmenting amount of the composition of claim 3.

4. A method for augmenting bone formation in an individual in need thereof which comprises administering to said individual a composition comprising a resorbable biopolymer selected from the group consisting of gelatin, cellulose, and collagen in combination with isolated mesenchymal stem cells.