Compositions, systems, and methods for combination therapies comprising fucosylated cells and chemokines and / or scaffold materials for autoimmune diseases and regenerative medicine.

Abstract

Compositions, drugs, systems, and kits comprising at least one ex vivo fucosylated cell type, at least one chemokine, and / or at least one matrix scaffold are disclosed. Methods for manufacturing and using these compositions, drugs, systems, and kits are also disclosed. In particular (but not limited to), methods for treating at least one autoimmune disease and methods for repairing tissue damage caused by injury or progressive disease are also disclosed.

Claims

1. A cell type fucosylated with at least one ex vivo dose effective for treatment, Including at least one chemokine, Drugs.

2. At least one cell type to be ex vivo fucosylated is selected from the group consisting of stem cells, cytotoxic T cells, regulatory T cells, helper T cells, NK cells, B cells, dendritic cells, macrophages, and combinations thereof. The drug according to claim 1.

3. The aforementioned at least one ex vivo fucosylated cell type includes ex vivo fucosylated stem cells, The drug according to claim 1.

4. The at least one cell type that is fucosylated ex vivo includes autologous cells, The drug according to claim 1.

5. The at least one cell type that is fucosylated ex vivo includes allogeneic cells. The drug according to claim 1.

6. The at least one chemokine is derived from a chemokine family selected from the CXC, CC, CX3C, and XC chemokine families. The drug according to claim 1.

7. The at least one chemokine is selected from the group consisting of CXCL12, CCL2, CCL5, CXCL10, CXCL8, and combinations thereof. The drug according to claim 1.

8. At least one chemokine is ex vivo fucosylated. The drug according to claim 1.

9. The at least one ex vivo fucosylated cell type comprises at least one ex vivo fucosylated stem cell, and the agent further comprises at least one immune cell type selected from the group consisting of cytotoxic T cells, regulatory T cells, helper T cells, NK cells, B cells, dendritic cells, macrophages, and combinations thereof. The drug according to claim 1.

10. The above-mentioned at least one immune cell type is ex vivo fucosylated. The drug according to claim 9.

11. Further including at least one matrix scaffold, The drug according to claim 1.

12. The at least one matrix scaffold is a fucoidan-based scaffold. The drug according to claim 11.

13. The scaffold comprises a cross-linked fucoidan-based scaffold. The drug according to claim 12.

14. A cell type fucosylated with at least one ex vivo dose effective for treatment, The system includes at least one matrix scaffold on which the at least one ex vivo fucosylated cell type is arranged. Drugs.

15. The at least one matrix scaffold is a fucoidan-based scaffold. The drug according to claim 14.

16. The scaffold comprises a cross-linked fucoidan-based scaffold. The drug according to claim 14.

17. For use in the treatment of at least one autoimmune disease, The agent according to any one of claims 1 to 16L.

18. The at least one autoimmune disease is selected from the group consisting of celiac disease, Crohn's disease (CD), type 1 diabetes, eczema / atopic dermatitis, endometriosis, lupus, Lyme disease, multiple sclerosis (MS), chronic fatigue syndrome (CFS), rheumatoid arthritis, ulcerative colitis (UC), and combinations thereof. The drug according to claim 17.

19. For use in repairing tissue damage caused by injury or progressive disease, The agent according to any one of claims 1 to 16L.

20. The tissue to be repaired is selected from a group consisting of the heart, bone, nervous system, skin, joints, liver, lungs, pancreas, reproductive system, kidneys, cancerous tissue, and combinations thereof. The drug according to claim 19 or 19A.

21. A drug comprising any one of claims 1 to 20, kit.

22. A method of treating the condition of a patient who requires treatment, The process includes administering the drug described in any one of claims 1 to 20 to a patient. method.

23. The aforementioned drug is approximately 10 ５ ~about 10 ７ The patient is injected with fucosylated cells at a dose of 1 kg / kg. The method according to claim 22.

24. The method described above is further defined as a method for treating at least one autoimmune disease. The method according to claim 22.

25. The at least one autoimmune disease is selected from the group consisting of celiac disease, Crohn's disease (CD), type 1 diabetes, eczema / atopic dermatitis, endometriosis, lupus, Lyme disease, multiple sclerosis (MS), chronic fatigue syndrome (CFS), rheumatoid arthritis, ulcerative colitis (UC), and combinations thereof. The method according to claim 24.

26. The method described above is further defined as a method for repairing tissue damage caused by injury or progressive disease. The method according to claim 22.

27. A method for preparing a drug, (1) A process of collecting cells from a subject of autologous, homogeneous, or heterogeneous origin, (2) A step of growing the cells, (3) A step of fucosyling at least a portion of the cells by contacting them with GDP-fucose and fucosyltransferase or a functional fragment of fucosyltransferase, and (4) A step of preparing a drug by combining fucosylated cells with at least one chemokine, method.

28. A method for preparing a hydrogel-containing drug for implantation in a patient, (1) A step of collecting cells of autologous, homogeneous, or heterogeneous origin from the subject, (2) A process of proliferating cells, (3) A step of fucosyling at least a portion of the cells by contacting them with GDP-fucose and fucosyltransferase or a functional fragment of fucosyltransferase, (4) The step of adding fucosylated cells to the hydrogel mixture, (5) A step of preparing a hydrogel-containing drug by adding a crosslinking agent, method.

29. The cell is a stem cell, and the process further includes activating the stem cell before adding it to the hydrogel. The method according to claim 28.

30. The hydrogel mixture contains fucoidan, and the crosslinking agent contains genipin. The method according to claim 28.

31. A method of treating patients who need treatment, (1) A step to identify patients who require hematopoietic stem cell transplantation (HSCT), (2) The process of collecting stem cells from the patient, (3) A process for proliferating stem cells, (4) A step of fucosyling at least a portion of the stem cells by contacting them with fucosyltransferase and GDP-fucose. (5) A step of forming a composition comprising fucosylated stem cells and at least one chemokine. (6) Exposing the patient to an immunosuppressant pretreatment regimen comprising at least one immunosuppressant, and (7) The step of injecting a patient with a composition comprising fucosylated stem cells and at least one chemokine, method.

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