Use of multipotent adult stem cells in treatment of myocardial infarction and congestive heart failure

• US 8,075,881 B2
• Filed: 06/13/2005
• Issued: 12/13/2011
• Est. Priority Date: 08/05/1999
• Status: Expired due to Fees

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Verfaillie, Catherine M., Reyes, Morayma, Furcht, Leo T.
• Primary Examiner(s): Lankford, Jr., Blaine
• Application Number:
  US11/151,689
• Publication Number:
  US 20060008450A1
• Time in Patent Office: 2,374 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2501/105 Insulin-like growth factors [IGF]
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/135 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2501/235 Leukemia inhibitory factor [LIF]
• CPC Class Codes: C12N 2501/33 Insulin
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/52 Fibronectin; Laminin
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The invention provides isolated stem cells of non-embryonic origin that can be maintained in culture in the undifferentiated state or differentiated to form cells of multiple tissue types. Also provided are methods of isolation and culture, as well as therapeutic uses for the isolated cells in cardiac indications.

Claims

1. A method of providing cardiac muscle to a subject in need thereof, said method comprising administering to the subject, in an amount effective to provide new cardiac muscle, isolated expanded human multipotent non-ES, non-germ, and non-embryonic germ cells that express telomerase and can differentiate into ectodermal, endodermal, and mesodermal cell types, wherein the existing cardiac muscle is damaged by disease or injury, wherein said telomerase-expressing cells were expanded in cell culture, and wherein said telomerase-expressing cells have undergone 10-40 cell doublings in culture.

4. The method of any of claims 1-3, wherein the disease is selected from the group consisting of congestive heart failure, coronary artery disease, myocardial infarction, myocardial isehemia, atherosclerosis, cardiomyopathy, idiopathic cardiomyopathy, cardiac arrhythmias, muscular dystrophy, muscle mass abnormality, muscle degeneration, infective myocarditis, drug- or toxin-induced muscle abnormalities, hypersensitivity myocarditis, autoimmune endocarditis, and congenital heart disease.

5. The method of any of claims 1-3, wherein the telomerase-expressing cells are administered using techniques selected from the group consisting of surgical intramyocardial injection, transendocardial injection, intracoronary injection, transvascular injection, intramuscular injection, intravenous injection and cardiac catheter administration.

6. The method of any of claims 1-3 wherein the telomerase-expressing cells have undergone 10 cell doublings.

7. The method of any of claims 1-3 wherein the telomerase-expressing cells have undergone 20 cell doublings.

8. The method of any of claims 1-3 wherein the telomerase-expressing cells have undergone 30 cell doublings.

9. The method of any of claims 1-3 wherein the telomerase-expressing cells have undergone 40 cell doublings.

10. The method of any of claims 1-3 wherein the telomerase-expressing cells further express oct3/4.

11. The method of any of claims 1-3 wherein the telomerase-expressing cells are allogeneic.

12. The method of any of claims 1-3 wherein the telomerase-expressing cells are autologous.

13. The method of claim 4 wherein the telomerase-expressing cells are administered to a subject with myocardial infarction.

14. The method of claim 4 wherein the telomerase-expressing cells are administered directly to the heart.

15. The method of claim 4 wherein the telomerase-expressing cells are administered systemically.

16. The method of claim 4 wherein the telomerase-expressing cells are administered by injection.

2. A method of increasing cardiac muscle function in a subject with existing cardiac muscle, said method comprising administering to the subject, in an amount effective to increase cardiac muscle function, isolated expanded human multipotent non-ES, non-germ, and non-embryonic germ cells that express telomerase and can differentiate into ectodermal, endodermal, and mesodermal cell types, wherein the existing cardiac muscle is damaged by disease or injury, wherein said telomerase-expressing cells were expanded in cell culture, and wherein said telomerase-expressing cells have undergone 10-40 cell doublings in culture.

3. A process for producing cardiac muscle cells in a subject, said method comprising administering to the subject, in proximity to existing cardiac muscle and in an amount effective to produce cardiac muscle cells, isolated expanded human multipotent non-ES, non-germ, and non-embryonic germ cells that express telomerase and can differentiate into ectodermal, endodermal, and mesodermal cell types, wherein the existing cardiac muscle is damaged by disease or injury, wherein said telomerase-expressing cells were expanded in cell culture, and wherein said telomerase-expressing cells have undergone 10-40 cell doublings in culture.