Pluripotent stem cell that induces repair and regeneration after myocardial infarction

• US 9,844,570 B2
• Filed: 08/15/2013
• Issued: 12/19/2017
• Est. Priority Date: 08/17/2012
• Status: Active Grant

• Current Assignee: Tohoku University National Universities Corporation
• Original Assignee: GIFU University, Clio, Inc. (Mitsubishi Chemical Group Corp.), Tohoku University National Universities Corporation
• Inventors: Yoshida, Masanori, Minatoguchi, Shinya, Dezawa, Mari
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US14/421,754
• Publication Number:
  US 20150196600A1
• Time in Patent Office: 1,587 Days
• 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 method for treating a myocardial infarction in a subject in need thereof, the method comprising:

administering to said subject a cell preparation containing a cell fraction comprising a population of pluripotent stem cells positive for SSEA-3, wherein the population of pluripotent stem cells is isolated from mesenchymal tissue or cultured mesenchymal cells by selecting for SSEA-3 positive cells, wherein the population of pluripotent stem cell is concentrated, wherein the pluripotent stem cells have a plurality of properties comprising;

(i) CD105-positivity;

(ii) low or absent telomerase activity;

(iii) ability to differentiate into embryonic endoderm, ectoderm, and mesoderm germ layers;

(iv) absence of neoplastic proliferation; and

(v) ability to self-renew, and wherein the size of the myocardial infarction in the subject is reduced in comparison to a control subject that did not receive said cell preparation, thereby treating a myocardial infarction in a subject in need thereof.

2. The method according to claim 1, wherein the pluripotent stem cells positive for SSEA-3 have been concentrated by external stress stimulation.

3. The method according to claim 1, wherein the subject has heart failure following serious massive myocardial infarction and wherein the subject is a human.

4. The method according to claim 1, wherein the pluripotent stem cells are CD117-negative and CD146-negative.

5. The method according to claim 1, wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.

6. The method according to claim 1, 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.

7. The method according to claim 1, wherein the pluripotent stem cells have the ability to integrate into the site of myocardial infarction.

8. The method according to claim 1, wherein the pluripotent stem cells have the ability to differentiate into myocardial cells.

9. The method according to claim 1, wherein the pluripotent stem cells have the ability to differentiate into vascular endothelial cells.

10. The method according to claim 1, wherein the cell preparation is administered into a vein or coronary artery of said subject within 1 month after said myocardial infarction one to ten times in a therapeutically effective amount of 1×

10³ cell to 1×

10⁶ cells.

11. The method according to claim 1, 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 value prior to myocardial infarction.

12. The method according to claim 1, wherein the cell preparation is administered into a vein or coronary artery of said subject within 1 month after said myocardial infarction in a therapeutically effective amount of 1.7×

10⁵ cells/kg body weight to 2.5×

10⁵ cells/kg body weight of the subject.

13. The method according to claim 2, wherein the external stress stimulation is a member selected from the group consisting of:

protease treatment, culturing under phosphate-deficient conditions, culturing under serum-deficient conditions, culturing under nutrient-deficient conditions, culturing under exposure to heat shock, culturing under mechanical stimulation, culturing under shaking treatment, culturing under pressure treatment and physical shock, and a combination of a plurality thereof.