Eluting matrix and uses thereof

Patent metadata

Field	Value
Publication number	US-10580262-B2
Application number	US-201715813917-A
Country	US
Kind code	B2
Filing date	Nov 15, 2017
Priority date	Nov 7, 2013
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

CXCL12 polypeptide eluting matrices encapsulating at least one cell are described for use in the treatment of autoimmune disorders.

First claim

We claim:

1. A method of providing a protein-expressing cell to a subject in need thereof, the method comprising implanting in the subject an eluting matrix comprising at least one protein-expressing-cell,
wherein the cell is encapsulated in a CXCL12-eluting porous polymeric-matrix which is permeable to the protein of the protein-expressing cell, and further
wherein the elution rate of CXCL12 from the matrix is at least about 1 ng/mL/hr so as to repel effector T-cells surrounding the matrix for a period of at least one month after implantation, thereby providing a protein-expressing cell to the subject.

2. The method of claim 1 , wherein the elution rate of CXCL12 is about 1 ng/mL/hr to about 3 ng/mL/hr.

3. The method of claim 1 , wherein the elution rate of CXCL12 is about 1.75 ng/mL/hr.

4. The method of claim 1 , wherein the CXCL12 is present in the matrix at a concentration of at least about 100 ng/mL.

5. The method of claim 1 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL.

6. The method of claim 5 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL for about 3 months to about 2 years after implantation.

7. The method of claim 1 , wherein the matrix has a thickness of from about 200 microns to about 500 microns.

8. The method of claim 1 , wherein the eluting matrix further comprises a layer of cells that express a CXCL12 polypeptide.

9. The method of claim 1 , wherein the eluting matrix further comprises an outer layer of a CXCL12 polypeptide.

10. The method of claim 1 , wherein the at least one protein-expressing cell is, selected from the group consisting of a myocyte, a fibroblast, a chondrocyte, a adipocyte, a fibromyoblast, an ectodermal cell, a kidney cell, a liver cell, a pancreatic cell, an intestinal cell, an osteoblast, and a hematopoietic cell.

11. The method of claim 1 , wherein the at least one protein-expressing cell is selected from the group consisting of a neuronal cell, a smooth muscle cell, a skeletal muscle cell, a cardiac cell, an epithelial, cell, and a hepatocyte.

12. The method of claim 1 , wherein the at least one protein-expressing cell is a stem cell.

13. The method of claim 1 , wherein the at least one protein-expressing cell is an islet cell that expresses insulin.

14. The method of claim 1 , wherein the subject has diabetes.

15. A method of providing an islet cell that expresses insulin to a subject in need thereof, the method comprising implanting in the subject an eluting matrix comprising at least one islet cell that expresses insulin,
wherein the cell is encapsulated in a CXCL12-eluting porous alginate matrix having a thickness of from about 200 microns to about 500 microns which is permeable to the insulin, and further
wherein the elution rate of CXCL12 from the matrix is at least about 1 ng/mL/hr so as to repel effector T-cells surrounding said matrix which is maintained for a period of at least one month after implantation,

thereby providing an islet cell that expresses insulin to the subject.

16. The method of claim 15 , wherein the islet cell is a xenogenic islet cell.

17. The method of claim 15 , wherein the elution rate of CXCL12 is about 1 ng/mL/hr to about 3 ng/mL/hr.

18. The method matrix of claim 15 , wherein the elution rate of CXCL12 is about 1.75 ng/mL/hr.

19. The method of claim 15 , wherein the CXCL12 is present in the matrix at a concentration of at least about 100 ng/mL.

20. The method of claim 15 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL.

21. The method of claim 15 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL for about 3 months to about 2 years after implantation.

22. The method of claim 15 , wherein the alginate matrix is covalently crosslinked.

23. The method of claim 15 , wherein the matrix comprises about 1.5 to about 2% w/v of a high mannuronic acid, calcium cross-linked alginate.

24. The method of claim 15 , wherein the alginate matrix is comprised of alginate polymer subunits having an average molecular weight of less than 75 kDa.

25. The method of claim 15 , wherein the alginate matrix is comprised of alginate polymer subunits having an average molecular weight of about 75 kDa to about 200 kDa.

26. The method of claim 15 , wherein the alginate matrix is comprised of mannuronic acid and guluronic acid.

27. The method of claim 26 , wherein the alginate matrix comprises a mannuronic acid to guluronic acid ratio of about 1:100 to about 100:1.

28. The method of claim 26 , wherein the alginate matrix comprises a guluronic acid to mannuronic acid ratio of no more than 3:2.

29. The method of claim 15 , wherein the subject has diabetes.

30. The method of claim 15 , wherein the at least one islet cell regulates blood glucose levels in the subject for a period of time.

31. The method of claim 30 , wherein the period of time is at least about 1 month.

32. The method of claim 30 , wherein the at least one islet cell maintains the fasting serum concentration of glucose in the subject at a blood level of between about 80 mg/dl and about 120 mg/dl.

33. The method of claim 30 , wherein the subject receives repeated implantation of the eluting matrix.

34. The method of claim 30 , wherein the eluting matrix is not degraded by effector T-cells or macrophages.

Assignees

• Massachusetts Gen Hospital

Inventors

• Poznansky Mark C
• Chen Tao

Classifications

• A63F2001/005

  Poker · CPC title

• A61K35/39

  Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36) · CPC title

• A61L27/38

  containing added animal cells (organs or tissue containing native cells A61L27/36) · CPC title

• G07F17/322

  Casino tables, e.g. tables having integrated screens, chip detection means · CPC title

• A63F1/00

  Card games · CPC title