Pharmaceutical composition including migratory factor for guiding pluripotent stem cells to injury
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.
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, wherein the compound 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)-3-methylimidazolindine-2,4,5-trione, 1-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-24(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.
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 1 , wherein activation of migration is guidance to a damaged site in the body.
4. The pharmaceutical composition according to claim 1 , wherein the pluripotent stem cells are SSEA3-positive.
5. The pharmaceutical composition according to claim 1 , wherein the pluripotent stem cells are CD105-positive.
6. The pharmaceutical composition according to of claim 1 , wherein the pluripotent stem cells are CD117-negative and CD146-negative.
7. The pharmaceutical composition according to claim 1 , wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.
8. The pharmaceutical composition 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.
9. The pharmaceutical composition according to claim 1 , 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.