SKELETAL MUSCLE AUGMENTATION UTILIZING MUSCLE-DERIVED PROGENITOR COMPOSITIONS, AND TREATMENTS THEREOF

• US 20090098094A1
• Filed: 10/03/2008
• Published: 04/16/2009
• Est. Priority Date: 05/01/1998
• Status: Active Grant

• Current Assignee: Michael Chancellor, Ronald Jankowski, Ryan Pruchnic, Thomas Payne
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Chancellor, Michael, Payne, Thomas, Jankowski, Ronald, Pruchnic, Ryan
• Granted Patent: US 9,499,791 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• 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: A61K 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2500/84 from mammals
• CPC Class Codes: C12N 2501/70 : Enzymes
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2510/02 : Cells for production
• CPC Class Codes: C12N 2533/54 : Collagen; Gelatin
• CPC Class Codes: C12N 5/0658 : Skeletal muscle cells, e.g. myocytes, myotubes, myoblasts
• CPC Class Codes: C12N 5/0659 : Satellite cells

Abstract

The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of soft tissue. Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, soft tissues in the treatment of various cosmetic or functional conditions, including malformation, injury, weakness, disease, or dysfunction. The invention also relates to novel uses of muscle-derived progenitor cells for the treatment of cosmetic or functional conditions, including, but not limited to skeletal muscle weakness, muscular dystrophy, muscle atrophy, spasticity, myoclonus and myalgia. The invention also relates to the novel use of MDCs for the increase of skeletal muscle mass in athletes or other organisms in need of greater than average skeletal muscle mass.

Claims

1. A method of augmenting a skeletal muscle in a mammal in need thereof comprising:

a) isolating MDCs;

b) expanding the isolated MDCs in culture between 10 and 20 days; and

c) administering a therapeutically effective portion of the expanded MDCs to the skeletal muscle in the mammal in need thereof;

thereby augmenting the skeletal muscle in the mammal in need thereof.

2. The method of claim 1, wherein the mammal in need thereof suffers from a muscle pathology.

3. The method of claim 1, wherein the mammal is a human.

4. The method of claim 1, wherein the MDCs are isolated by a method comprising:

(a) suspending human skeletal muscle cells in a first cell culture container between 30 and 120 minutes;

(b) transferring the media from the first cell culture container to a second cell culture container;

(c) allowing the remaining cells in the media to attach to the walls of the second cell culture container; and

(d) isolating the cells from the walls of the second cell culture container, wherein the isolated cells are MDCs;

thereby isolating the MDCs.

5. The method of claim 1, wherein the MDCs are isolated by a method comprising:

(a) plating a suspension of skeletal muscle cells from skeletal muscle tissue in a first container to which fibroblast cells of the skeletal muscle cell suspension adhere,

(b) re-plating non-adherent cells from step (a) in a second container, wherein the step of re-plating is after about 15 to about 20% of cells have adhered to the first container; and

(c) repeating step (b) at least once;

thereby isolating the MDCs.

6. The method of claim 1, wherein the MDCs are administered by injecting the MDCs into the skeletal muscle of the mammal.

7. The method of claim 1, wherein the muscle of the mammal has a defect.

8. The method of claim 1, wherein the MDCs are administered by applying them to the defect.

9. The method of claim 8, wherein the MDCs are applied through injection.

10. A method of augmenting a skeletal muscle in a mammal in need thereof comprising:

a) isolating MDCs;

b) freezing the isolated MDCs to a temperature between about −

25°

C. and −

90°

C.;

c) thawing the frozen isolated MDCs; and

d) administering the thawed MDCs to the skeletal muscle in the mammal in need thereof;

thereby augmenting the skeletal muscle in the mammal in need thereof.

11. The method of claim 10, wherein the mammal in need thereof suffers from a muscle pathology.

12. The method of claim 10, wherein the mammal is a human.

13. The method of claim 10, wherein the MDCs are isolated by a method comprising:

(a) suspending human skeletal muscle cells in a first cell culture container between 30 and 120 minutes;

(b) transferring the media from the first cell culture container to a second cell culture container;

(c) allowing the remaining cells in the media to attach to the walls of the second cell culture container; and

(d) isolating the cells from the walls of the second cell culture container, wherein the isolated cells are MDCs;

thereby isolating the MDCs.

14. The method of claim 10, wherein the MDCs are isolated by a method comprising:

(a) plating a suspension of skeletal muscle cells from skeletal muscle tissue in a first container to which fibroblast cells of the skeletal muscle cell suspension adhere,

(b) re-plating non-adherent cells from step (a) in a second container, wherein the step of re-plating is after about 15 to about 20% of cells have adhered to the first container; and

(c) repeating step (b) at least once;

thereby isolating the MDCs.

15. The method of claim 10, wherein the MDCs are administered by injecting the MDCs into the skeletal muscle of the mammal.

16. The method of claim 10, wherein the muscle of the mammal has a defect.

17. The method of claim 10, wherein the MDCs are administered by applying them to the defect.

18. The method of claim 17, wherein the MDCs are applied through injection.