Protein delivery from stem cell microcarriers

• US 10,441,610 B2
• Filed: 11/23/2011
• Issued: 10/15/2019
• Est. Priority Date: 11/23/2010
• Status: Active Grant

• Current Assignee: Georgia Institute of Technology (University System of Georgia)
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Boyan, Barbara Dale, Schwartz, Zvi, Lee, Christopher S. D., Leslie, Shirae Kerisha, Kinney, Ramsey C.
• Primary Examiner(s): Belyavskyi, Michail A
• Application Number:
  US13/988,929
• Publication Number:
  US 20140370111A1
• Time in Patent Office: 2,883 Days
• Field of Search: None
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/32 Amino acids
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2501/15 Transforming growth factor beta (TGF-β)
• 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 2533/74 Alginate
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

Disclosed are methods and compositions of microbead carriers for delivery of cells and other biologically active substances to diseased or damaged tissue in a subject in need thereof.

Claims

1. A composition for affecting chondrogenic gene expression when contacting a chondrocyte comprising injectable biodegradable polymeric hydrogel controlled-release microbeads, wherein the microbeads comprise mesenchymal stem cells and alginate, wherein alginate lyase is incorporated into the alginate, and wherein the expression, production, or secretion of an angiogenic factor or a hypertrophic factor or both by the mesenchymal stem cells is inhibited by contact with chondrogenic medium, or the expression, production, or secretion of a chondrogenic factor or an anti-hypertrophic factor or both by the mesenchymal stem cells is stimulated by contact with chondrogenic medium, and wherein the mesenchymal stem cells are obtainable by contact with a chondrogenic medium for 5 days.

2. The composition of claim 1, wherein the microbeads are about 200 micrometers or less in diameter.

3. The composition of claim 1, wherein the mesenchymal stem cells are adipose stem cells.

4. The composition of claim 3, wherein the angiogenic factor is VEGF-A or FGF-2, or a combination of both.

5. The composition of claim 3, wherein the hypertrophic factor is FGF-18.

6. The composition of claim 3, wherein the chondrogenic factor is TGF-β

1, TGF-β

2, TGF-β

3, IGF-1, or PTHrP, or a combination thereof.

7. The composition of claim 3, wherein the anti-hypertrophic factor is Noggin.

8. The composition of claim 1, wherein the microbeads are a renewable reservoir for the angiogenic factor, hypertrophic factor, chondrogenic factor, or anti-hypertrophic factor, or a combination thereof, which are expressed, produced, or secreted by the mesenchymal stem cells.

9. The composition of claim 8, wherein the mesenchymal stem cells are adipose stem cells.

10. The composition of claim 1, wherein the mesenchymal stem cells are are conditioned with chondrogenic medium before the stem cells are encapsulated in the microbeads.

11. The composition of claim 1, wherein the mesenchymal stem cells are conditioned with chondrogenic medium after the stem cells are encapsulated in the microbeads.