Pluripotent stem cell that induces repair and regeneration after myocardial infarction

Patent metadata

Field	Value
Publication number	US-2018050067-A1
Application number	US-201715802899-A
Country	US
Kind code	A1
Filing date	Nov 3, 2017
Priority date	Aug 17, 2012
Publication date	Feb 22, 2018
Grant date	—

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.

First claim

1 . A method for treating myocardial infarction in a subject in need thereof, the method comprising: administering a cell preparation comprising pluripotent stem cells positive for SSEA-3 isolated from biological mesenchymal tissue or cultured mesenchymal cells to thereby treat the myocardial infarction.

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

3 . The method according to claim 1 for treatment of heart failure following serious massive myocardial infarction in a human.

4 . The method according to claim 1 , wherein the pluripotent stem cells are CD105-positive.

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

6 . 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.

7 . 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.

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

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

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

12 . The method according to claim 1 , 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 1×10 3 cells/individual to 1×10 6 cells/individual.

13 . 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 normal values.

14 . The method according to claim 2 , wherein the external stress stimulation is a member selected from a group consisting of protease treatment, culturing under oxygen-deficient conditions, culturing under phosphate-deficient conditions, culturing under serum-deficient conditions, culturing under poor nutritional 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.

15 . 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 ischemia in a therapeutically effective amount of 1.7×10 5 cells/kg to 2.5×10 5 cells/kg per individual mammal based on body weight.

Assignees

• Clio Inc
• Univ Gifu
• Univ Tohoku

Inventors

• Yoshida Masanori
• Minatoguchi Shinya
• Dezawa Mari

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K35/28 Primary

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• A61K9/0019

  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 title

• C12N2506/03

  from non-embryonic pluripotent stem cells · CPC title

• C12N5/0607

  Non-embryonic pluripotent stem cells, e.g. MASC (induced pluripotent stem cells C12N5/0696) · CPC title