# US 10,441,610 B2 · Protein delivery from stem cell microcarriers

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- Number: US 10,441,610 B2
- Document ID: US10441610B2
- Status: Granted
- Kind: B2
- Application number: 13/988,929
- Filed: 2011-11-23
- Published: 2014-12-18
- Granted: 2019-10-15
- Earliest claimed: 2010-11-23
- Assignees: Georgia Tech Research Corporation
- Applicants: Barbara Dale Boyan; Zvi Schwartz; Christopher S. D. Lee; Shirae Kerisha Leslie; Ramsey C. Kinney
- Inventors: Barbara Dale Boyan; Zvi Schwartz; Christopher S. D. Lee; Shirae Kerisha Leslie; Ramsey C. Kinney
- Web page: https://patentgrep.com/patent/US10441610B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 9/5036: {Polysaccharides, e.g. gums, alginate; Cyclodextrin}
- A61P 19/00: Drugs for skeletal disorders
- C12N 5/0655: {Chondrocytes; Cartilage}
- C12N 5/0667: {Adipose-derived stem cells [ADSC]; Adipose stromal stem cells}
- A61K 2035/128: {capsules, e.g. microcapsules}
- C12N 2500/25: Insulin-transferrin; Insulin-transferrin-selenium
- C12N 2500/32: Amino acids
- C12N 2500/34: Sugars
- C12N 2500/38: Vitamins
- C12N 2501/15: Transforming growth factor beta (TGF-β)
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/39: Steroid hormones
- C12N 2533/74: Alginate
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

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

### Claim 5 (depends on 3)

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

### Claim 6 (depends on 3)

The composition of claim 3, wherein the chondrogenic factor is TGF-β1, TGF-β2, TGF-β3, IGF-1, or PTHrP, or a combination thereof.

### Claim 7 (depends on 3)

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

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 8)

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

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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