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

Patent metadata

Field	Value
Publication number	US-2016008340-A1
Application number	US-201414771588-A
Country	US
Kind code	A1
Filing date	Feb 28, 2014
Priority date	Mar 1, 2013
Publication date	Jan 14, 2016
Grant date	—

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

1 . A pharmaceutical composition for activating migration of pluripotent stem cells, comprising: a compound that activates sphingosine-1-phosphate receptor 2 as an active ingredient thereof.

2 . The pharmaceutical composition according to claim 1 , wherein the compound that activates sphingosine-1-phosphate receptor 2 is an agonist of sphingosine-1-phosphate receptor 2.

3 . The pharmaceutical composition according to claim 2 , wherein the agonist of sphingosine-1-phosphate receptor 2 is sphingosine-1-phosphate or a derivative thereof.

4 . The pharmaceutical composition according to claim 2 , wherein the agonist of sphingosine-1-phosphate receptor 2 is selected from the group consisting of 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)-5-(trifluoromethyl) pyridin-2(1H)-one, 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)pyrrolidine-2,5-dione, 1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl)-3-methylimidazolindine-2,4,5-trione, 1-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-((1-methyl-1H-tetrazol-5-yl)thio)ethanone, and (S)-1-(2-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-oxoethyl-2′, 3′-dihydrospiro[imidazolidine-4,1′-indene]-2,5-dione.

5 . The pharmaceutical composition according to claim 1 , wherein the compound that activates sphingosine-1-phosphate receptor 2 is a sphingosine-1-phosphate lyase inhibitor.

6 . The pharmaceutical composition according to claim 5 , wherein the sphinigosine-1-phosphate lyase inhibitor is selected from the group consisting of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime, (1R,2S,3R)-1-(2-isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol, and 1-(5-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone.

7 . The pharmaceutical composition according to any of claims 1 to 6 , wherein activation of migration is guidance to a damaged site in the body.

8 . The pharmaceutical composition according to any of claims 1 to 7 , wherein the pluripotent stem cells are SSEA3-positive.

9 . The pharmaceutical composition according to any of claims 1 to 8 , wherein the pluripotent stem cells are CD105-positive.

10 . The pharmaceutical composition according to any of claims 1 to 9 , wherein the pluripotent stem cells are CD117-negative and CD146-negative.

11 . The pharmaceutical composition according to any of claims 1 to 10 , wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.

12 . The pharmaceutical composition according to any of claims 1 to 11 , wherein the pluripotent stem cells are CD34-negative, CD117-negative, CD146-negative, CD271-negative, NG2-negative, vWF-negative, Sox10-negative, Snail-negative, Slug-negative, Tyrpl-negative and Dct-negative.

13 . The pharmaceutical composition according to any of claims 1 to 12 , wherein the pluripotent stem cells are pluripotent stem cells having 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.

Assignees

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

Inventors

• Dezawa Mari
• Fujiyoshi Yoshinori
• Yoshida Masanori

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• 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

• 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