Pluripotent stem cell for treatment of cerebral infarction
View Patent ↗An object of the present invention is to provide a novel medical application to regenerative medicine that uses pluripotent stem cells (Muse cells). The present invention provides a cell preparation for treating cerebral infarction and sequelae associated therewith that contains SSEA-3-positive pluripotent stem cells isolated from mesenchymal tissue in the body or cultured mesenchymal cells. The cell preparation of the present invention is based on a brain tissue regeneration mechanism by which Muse cells differentiate into nerve cells and the like in damaged brain tissue by administering Muse cells into cerebral parenchyma.
1. A method for treating sequelae from a cerebral infarction in a mammalian subject in need thereof, the method comprising:
administering a cell preparation containing human pluripotent stem cells positive for SSEA-3 isolated from human mesenchymal tissue or cultured human mesenchymal cells to the mammalian subject wherein said pluripotent stem cells have a plurality of properties, said plurality of properties comprising:
(i) CD 105-positively;
(ii) low or absent telomerase activity;
(iii) ability to differentiate into any of the three germ layers;
(iv) absence of demonstration of neoplastic proliferation;
(v) self-renewal ability;
wherein the sequelae is selected from the group consisting of speech and language disorder, disturbance of perception such as numbness, disorder of movement in a limb, headache, vomiting, visual loss, deglutition disorder, articulation disorder, and dementia; and
wherein said pluripotent stem cells are administered 1 to 10 times at 1×10 3 cells to 2×10 7 cells per individual, or the total individual doses of said pluripotent stem cells are 1×10 3 cells to 2×10 8 cells or 1×10 4 cells to 1×10 8 cells, to treat sequelae from the cerebral infarction.
2. The method according to claim 1 , wherein the pluripotent stem cells positive for SSEA-3 contain a concentrated cell fraction as a result of stimulation by external stress.
3. The method according to claim 1 , wherein the pluripotent stem cells are CD117-negative and CD146-negative.
4. 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.
5. 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, Tyrpl-negative and Dct-negative.
6. The method according to claim 1 , wherein the pluripotent stem cells have the ability to differentiate into one or more cells selected from the group consisting of nerve cells, glial cells, vascular endothelial cells, and/or microglial cells.
7. The method according to claim 1 , wherein the cell preparation containing the pluripotent stem cells reduces infarct size by a mechanism involving regeneration of brain tissue.
8. The method according to claim 1 , wherein the cell preparation containing the pluripotent stem cells improves or restores a brain dysfunction due to cerebral infarction by a mechanism involving regeneration of brain tissue.
9. A method for treating sequelae from a cerebral infarction in a mammalian subject in need thereof, the method comprising:
administering to cerebral parenchyma of the mammalian subject a cell preparation containing human pluripotent stem cells positive for SSEA-3 isolated from human mesenchymal tissue or cultured human mesenchymal cells to the mammalian subject, wherein said pluripotent stem cells have a plurality of properties, said plurality of properties comprising:
(i) CD105-positively;
(ii) low or absent telomerase activity;
(iii) ability to differentiate into any of the three germ layers;
(iv) absence of demonstration of neoplastic proliferation;
(v) self-renewal ability, wherein the sequelae is selected from the group consisting of speech and language disorder, disturbance of perception such as numbness, disorder of movement in a limb, headache, vomiting, visual loss, deglutition disorder, articulation disorder, and dementia; and
wherein said pluripotent stem cells are administered 1 to 10 times at 1×10 3 cells to 2×10 7 cells per individual, or the total individual doses of said pluripotent stem cells are 1×10 3 cells to 2×10 8 cells or 1×10 4 cells to 1×10 8 cells, to treat sequelae from the cerebral infarction.
10. The method according to claim 9 , wherein the pluripotent stem cells positive for SSEA-3 contain a concentrated cell fraction as a result of stimulation by external stress.
11. The method according to claim 9 , wherein the pluripotent stem cells are CD117-negative and CD146-negative.
12. The method according to claim 9 , wherein the pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.
13. The method according to claim 9 , 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.
14. The method according to claim 9 , wherein the pluripotent stem cells have the ability to differentiate into one or more cells selected from the group consisting of nerve cells, glial cells, vascular endothelial cells, and/or microglial cells.
15. The method according to claim 9 , wherein the cell preparation containing the pluripotent stem cells reduces infarct size by a mechanism involving regeneration of brain tissue.
16. The method according to claim 9 , wherein the cell preparation containing the pluripotent stem cells improves or restores a brain dysfunction due to cerebral infarction by a mechanism involving regeneration of brain tissue.
17. The method according to claim 1 , wherein the cell preparation containing the pluripotent stem cells is administered to cerebral parenchyma and accumulate in a region bordering the infarction and differentiate into nerve cells.
18. The method according to claim 9 , wherein the cell preparation containing the pluripotent stem cells accumulate in a region bordering the infarction and differentiate into nerve cells.
19. The method according to claim 1 , wherein the mammalian subject is a human.
20. The method according to claim 9 , wherein the mammalian subject is a human.
21. The method according to claim 1 , wherein the administration of the cell preparation improves motor function of the mammalian subject.
22. The method according to claim 9 , wherein the administration of the cell preparation improves motor function of the mammalian subject.
23. The method according to claim 1 , wherein the administration of the cell preparation is administered within 3 to 48 hours of infarction onset.
24. The method according to claim 9 , wherein the administration of the cell preparation is administered within 3 to 48 hours of infarction onset.