PLURIPOTENT STEM CELL THAT INDUCES REPAIR AND REGENERATION AFTER MYOCARDIAL INFARCTION

• US 20150196600A1
• Filed: 08/15/2013
• Published: 07/16/2015
• Est. Priority Date: 08/17/2012
• Status: Active Grant

• Current Assignee: National University Corporation Tokai National Higher Education And Research System, Tohoku University National Universities Corporation
• Original Assignee: Tohoku University National Universities Corporation
• Inventors: Minatoguchi, Shinya, Dezawa, Mari, Yoshida, Masanori
• Granted Patent: US 9,844,570 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

An object of the present invention is to provide a novel medical application for use in regenerative medicine that uses pluripotent stem cells (Muse cells). The present invention provides a cell preparation for treating myocardial infarction, and particularly serious massive myocardial infarction and heart failure associated therewith, that contains pluripotent stem cells positive for SSEA-3 isolated from biological mesenchymal tissue or cultured mesenchymal cells. The cell preparation of the present invention is based on a cardiac tissue regeneration mechanism by which Muse cells are made to selectively accumulate in damaged myocardial tissue and differentiate into cardiac muscle in that tissue as a result of intravenous administration of Muse cells to a subject presenting with the aforementioned disorders.

Claims

1. A cell preparation for treating myocardial infarction, comprising:

pluripotent stem cells positive for SSEA-3 isolated from biological mesenchymal tissue or cultured mesenchymal cells.

2. The cell preparation according to claim 1, wherein the pluripotent stem cells positive for SSEA-3 contain a concentrated cell fraction as a result of stimulation by external stress.

3. The cell preparation according to claim 1 or 2 for prevention and/or treatment of heart failure following serious massive myocardial infarction in humans.

4. The cell preparation according to any one of claims 1 to 3, wherein the pluripotent stem cells are CD105-positive.

5. The cell preparation according to any one of claims 1 to 4, wherein the pluripotent stem cells are CD117-negative and CD146-negative.

6. The cell preparation according to any one of claims 1 to 5, wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.

7. The cell preparation according to any one of claims 1 to 6, wherein the pluripotent stem cells are CD34-negative, CD117-negative, CD146-negative, CD271-negative, NG2-negative, vWF-negative, Sox10-negative, Snail-negative, Slug-negative, Tyrp1-negative and Dct-negative.

8. The cell preparation according to any one of claims 1 to 7, wherein the pluripotent stem cells are pluripotent stem cells having all of the properties indicated below:

(i) low or absent telomerase activity;

(ii) ability to differentiate into any of the three germ layers;

(iii) absence of demonstration of neoplastic proliferation; and

,

(iv) self-renewal ability.

9. The cell preparation according to any one of claims 1 to 8, wherein the pluripotent stem cells have the ability to integrate into the site of myocardial infarction.

10. The cell preparation according to any one of claims 1 to 9, wherein the pluripotent stem cells have the ability to differentiate into myocardial cells.

11. The cell preparation according to any one of claims 1 to 9, wherein the pluripotent stem cells have the ability to differentiate into vascular endothelial cells.

12. The cell preparation according to any one of claims 1 to 11, wherein the pluripotent stem cells are administered into a vein or coronary artery of a subject within 1 month after ischemia one to ten times in a therapeutically effective amount of 1×

10³ cells/individual to 1×

10⁶ cells/individual.

13. The cell preparation according to any one of claims 1 to 12, wherein the size of the myocardial infarct is reduced in comparison with a non-administered control.

14. The cell preparation according to any one of claims 1 to 13, wherein at least one cardiac function indicator, selected from the group consisting of change in left ventricular pressure over time, left ventricular end-diastolic dimension (LVDd), ejection fraction (EF), left ventricular fractional shortening (FS) and left ventricular end-systolic dimension (LVDs), is restored to the normal value.