OPTIMIZATION OF ALGINATE ENCAPSULATION OF ISLETS FOR TRANSPLANTATION

• US 20110165219A1
• Filed: 09/16/2009
• Published: 07/07/2011
• Est. Priority Date: 09/17/2008
• Status: Active Grant

• Current Assignee: Beta Cell Technologies Pty., Ltd.
• Original Assignee: Beta Cell Technologies Pty., Ltd.
• Inventors: Rotem, Avi, Gendler, Zohar, Azarov, Dimitry, Barkai, Uriel, Neufeld, Tova
• Granted Patent: US 9,540,630 B2
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 11/10 the carrier being a carbohydrate
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

Apparatus is provided, including a plurality of islets, and a hydrogel configured to macroencapsulate the plurality of islets. The hydrogel is implantable in a subcapsular space (21) of a kidney (22) of a subject and is shaped to define a planar configuration. Other applications are also described.

Claims

1. Apparatus, comprising:

a plurality of islets; and

a hydrogel configured to macroencapsulate the plurality of islets, the hydrogel being implantable in a subcapsular space of a kidney of a subject, and shaped to define a planar configuration.

2. The apparatus according to claim 1, further comprising at least one semi-permeable membrane covering at least a portion of the hydrogel.

3. The apparatus according to claim 1, wherein the plurality of cells has a density of 2,000-8,000 islets/cm̂

2.

4. The apparatus according to claim 1, further comprising at least one semi-permeable membrane disposed at least in part within at least a portion of the hydrogel.

5. The apparatus according to claim 1, wherein the hydrogel is configured to be implanted in the subcapsular space of the kidney using laparoscopy.

6. The apparatus according to claim 1, wherein the hydrogel is configured to be removed from the subcapsular space of the kidney using laparoscopy.

7. The apparatus according to claim 1, wherein the hydrogel comprises constituents of extracellular matrix.

8. The apparatus according to claim 1, wherein the hydrogel comprises collagen.

9. The apparatus according to claim 1, wherein the hydrogel comprises laminin.

10. The apparatus according to claim 1, wherein the hydrogel comprises mesenchymal stem cells.

11. The apparatus according to claim 1, wherein the plurality of islets comprises 80,000-4,000,000 islets.

12. The apparatus according to claim 11, wherein the plurality of islets comprises 200,000-800,000 islets.

13. The apparatus according to claim 1, wherein the hydrogel comprises alginate, and wherein the alginate has a concentration of guluronic acid of between 30% and 50%.

14. The apparatus according to claim 13, wherein the concentration of guluronic acid is between 40% and 47%.

15. The apparatus according to claim 13, wherein the alginate has a dry matter content of at least 1.6%.

16. The apparatus according to claim 13, wherein the alginate has a dry matter content of at least 2.1%.

17. The apparatus according to claim 13, wherein the alginate is cross-linked with strontium.

18. A method, comprising:

providing a plurality of islets macroencapsulated in a hydrogel shaped to define a planar configuration; and

implanting the macroencapsulated islets in a subcapsular space of a kidney of a subject.

19. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that is covered at least in part by a semi-permeable membrane.

20. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel and in a semi-permeable membrane that is disposed at least in part within the hydrogel.

21. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing a plurality of islets having a density of 2,000-8,000 islets/cm̂

2.

22. The method according to claim 18, wherein implanting the macroencapsulated islets in the subcapsular space of the kidney comprises implanting the macroencapsulated islets in the subcapsular space of the kidney using laparoscopy.

23. The method according to claim 18, further comprising removing the macroencapsulated islets from the subcapsular space of the kidney using laparoscopy.

24. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises constituents of extracellular matrix.

25. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises collagen.

26. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises encapsulating the plurality of islets in a hydrogel that comprises laminin.

27. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises mesenchymal stem cells.

28. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing 80,000-4,000,000 islets.

29. The method according to claim 28, wherein providing the plurality of islets in the hydrogel comprises providing 200,000-800,000 islets.

30. The method according to claim 18, wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in alginate having a concentration of guluronic acid of between 30% and 50%.

31. The method according to claim 30, wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a concentration of guluronic acid of between 40% and 47%.

32. The method according to claim 30, wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a dry matter content of at least 1.6%.

33. The method according to claim 30, wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a dry matter content of at least 2.1%.

34. The method according to claim 30, wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate that is cross-linked with strontium.

35. A method, comprising:

providing a plurality of islets macroencapsulated in a hydrogel shaped to define a planar configuration; and

implanting the macroencapsulated islets in at least one area of a body of a subject selected from the group consisting of;

a liver of the subject, an area in a vicinity of a diaphragm of the subject, and an omental pouch of the subject.

36. Apparatus, comprising:

a plurality of islets having a density of 2,000-8,000 islets/cm̂

2;

an alginate structure having a planar configuration that macroencapsulates the plurality of islets, the structure configured to be implanted in a subcapsular space of a kidney of a subject, and having;

a longest dimension between 30 mm and 120 mm,

a dry matter content of at least 1.6%, and

a concentration of guluronic acid of between 40% and 50%.

37. The apparatus according to claim 36, wherein the dry matter content of alginate in the alginate structure is between 2.1% and 5.0%.

38. The apparatus according to claim 36, wherein the concentration of guluronic acid is between 40% and 47%.

39. The apparatus according to claim 36, wherein the plurality of islets comprises 200,000-800,000 islets.

40. A method, comprising:

providing a plurality of islets having a density of 2,000-8,000 islets/cm̂

2 macroencapsulated in an alginate structure having;

a planar configuration,

a longest dimension between 30 mm and 120 mm,

a dry matter content of at least 1.6%, and

a concentration of guluronic acid of between 40% and 50%; and

implanting in a subcapsular space of a kidney of a subject the alginate structure that macroencapsulates the plurality of islets.

41. The method according to claim 40, wherein providing the plurality of islets in the alginate structure comprises providing the plurality of islets in an alginate structure having a dry matter content of between 2.1% and 5.0%.

42. The method according to claim 40, wherein providing the plurality of islets in the alginate structure comprises providing the plurality of islets in an alginate structure having a concentration of guluronic acid between 40% and 47%.

43. The method according to claim 40, wherein providing the plurality of islets in the alginate structure comprises providing 200,000-800,000 islets.