Pharmaceutical composition including migratory factor for guiding pluripotent stem cells to damage

Patent metadata

Field	Value
Publication number	US-10369162-B2
Application number	US-201715642534-A
Country	US
Kind code	B2
Filing date	Jul 6, 2017
Priority date	Mar 1, 2013
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

The purpose of the present invention is to identify a migratory factor that guides pluripotent stem cells (Muse cells) useful in new medical applications to damage, and to provide a pharmaceutical composition that includes the migratory factor for promoting tissue regeneration in regenerative medicine that makes use of Muse cells. In the present invention, a receptor that is specifically expressed in Muse cells rather than non-Muse cells was identified, and it was confirmed that a ligand for this receptor can function as a migratory factor. In the present invention, sphingosine-1-phosphate (S1P) was identified as a migratory factor, and thus, the present invention pertains to a pharmaceutical composition for guiding pluripotent stem cells to damage, the composition including S1P as an active ingredient.

First claim

The invention claimed is:

1. A method for activating migration of pluripotent stem cells, the method comprising: administering to a subject an agonist of sphingosine-1-phosphate receptor 2 as an active ingredient thereof, wherein the pluripotent stem cells are SSEA3-positive and CD105-positive and further have all of the following properties:
(i) low or absent telomerase activity;
(ii) ability to differentiate into cells of any of the three germ layers;
(iii) absence of demonstration of neoplastic proliferation; and
(iv) presence of self-renewal ability,
wherein the agonist of sphingosine-1-phosphate receptor 2 is 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethy)ppyrrolidine-2,5-dione.

2. A method for enhancing guidance of pluripotent stem cells to a damaged site in the body, the method comprising: administering to a subject an agonist of sphingosine-1-phosphate receptor 2 as an active ingredient thereof, wherein the pluripotent stem cells are SSEA3-positive and CD105-positive and further have all of the following properties:
(i) low or absent telomerase activity;
(ii) ability to differentiate into cells of any of the three germ layers;
(iii) absence of demonstration of neoplastic proliferation; and
(iv) presence of self-renewal ability,
wherein the agonist of sphingosine-1-phosphate receptor 2 is 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)pyrrolidine-2,5-dione.

3. A method for enhancing therapeutic effects in tissue regeneration by pluripotent stem cells, the method comprising: administering to a subject an agonist of sphingosine-1-phosphate receptor 2 as an active ingredient thereof, wherein the pluripotent stem cells are SSEA3-positive and CD105-positive and further have all of the following properties:
(i) low or absent telomerase activity;
(ii) ability to differentiate into cells of any of the three germ layers;
(iii) absence of demonstration of neoplastic proliferation; and
(iv) presence of self-renewal ability,
wherein the agonist of sphingosine-1-phosphate receptor 2 is 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)pyrrolidine-2,5-dione.

4. The method of any one of claims 1 to 3 , wherein the pluripotent stem cells are CD117-negative and CD146-negative.

5. The method of any one of claims 1 to 3 , wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.

6. The method of any one of claims 1 to 3 , 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.

Assignees

• Clio Inc
• Univ Tohoku
• Univ Nagoya Nat Univ Corp

Inventors

• Dezawa Mari
• Fujiyoshi Yoshinori
• Yoshida Masanori

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• 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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title