Skeletal muscle augmentation utilizing muscle-derived progenitor compositions, and treatments thereof

• US 9,499,791 B2
• Filed: 10/03/2008
• Issued: 11/22/2016
• Est. Priority Date: 05/01/1998
• Status: Active Grant

• Current Assignee: Cook Myosite, University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Payne, Thomas, Jankowski, Ronald, Pruchnic, Ryan, Chancellor, Michael
• Primary Examiner(s): Moloye, Titilayo
• Application Number:
  US12/245,379
• Publication Number:
  US 20090098094A1
• Time in Patent Office: 2,972 Days
• US Class Current: 1/1
• 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 (MDCs) that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction into a site of soft tissue. Also provided are methods of isolating MDCs. The invention further provides methods of using compositions comprising MDCs 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 uses of MDCs 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 use of MDCs for the increase of skeletal muscle.

Claims

1. A method of augmenting a skeletal muscle in a mammal suffering from a muscle pathology comprising:

a) isolating muscle-derived progenitor cells (MDCs) by a method comprising;

(i) isolating skeletal muscle from a human;

(ii) storing the skeletal muscle at 4°

C. for 5 to 7 days;

(iii) suspending the human skeletal muscle in a medium in a first cell culture container between 30 and 120 minutes thereby producing a cell population of adherent cells and a population of non-adherent cells;

(iv) isolating the medium containing a population of non-adherent cells;

(v) transferring the medium containing the population of the non-adherent cells to a second cell culture container;

(vi) allowing the population of the transferred non-adherent cells from step (v) to attach to the walls of the second cell culture container, wherein the incubation is for 1 to 3 days;

(vii) removing the medium from the second container and replacing with new medium after the 1 to 3 days of incubation; and

(viii) isolating the cells from the walls of the second cell culture container, wherein the isolated cells are MDCs and are desmin+;

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

c) administering a therapeutically effective amount of the expanded MDCs to the skeletal muscle in the mammal suffering from a muscle pathology;

allowing the MDCS to engraft to the skeletal muscle and thereby augmenting the skeletal muscle in the mammal.

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

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

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

5. The method of claim 4, wherein the expanded MDCs are administered by applying them onto, into or around the site of the defect.

6. The method of claim 5, wherein the expanded MDCs are applied through injection.

7. A method of augmenting a skeletal muscle in a mammal suffering from a muscle pathology comprising:

a) isolating muscle-derived progenitor cells (MDCs) by a method comprising;

(i) isolating skeletal muscle from a human;

(ii) storing the skeletal muscle at 4°

C. for 5 to 7 days;

(iii) suspending the human skeletal muscle in a medium in a first cell culture container between 30 and 120 minutes thereby producing a cell population of adherent cells and a population of non-adherent cells;

(iv) isolating the medium containing a population of non-adherent cells;

(v) transferring the medium containing the population of the non-adherent cells to a second cell culture container;

(vi) allowing the population of the transferred non-adherent cells from step (v) to attach to the walls of the second cell culture container, wherein the incubation is for 1 to 3 days;

(vii) removing the medium from the second container and replacing with new medium after the 1 to 3 days of incubation; and

(viii) isolating the cells from the walls of the second cell culture container, wherein the isolated cells are MDCs and are desmin+;

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

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

25°

C. and −

90°

C.;

d) thawing the frozen isolated MDCs at room temperature with an equal volume of physiologic saline;

and e) administering the thawed MDCs to the skeletal muscle in the mammal suffering from a muscle pathology;

allowing the MDCS to engraft to the skeletal muscle and thereby augmenting the skeletal muscle in the mammal.

8. The method of claim 7, wherein the mammal is a human.

9. The method of claim 7, wherein the expanded MDCs are administered by injecting the MDCs into the skeletal muscle of the mammal.

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

11. The method of claim 10, wherein the expanded MDCs are administered by applying them onto, into or around the site of the defect.

12. The method of claim 11, wherein the MDCs are applied through injection.