Cell carrier and cell carrier containment devices containing regenerative cells

• US 20050058632A1
• Filed: 07/01/2004
• Published: 03/17/2005
• Est. Priority Date: 12/07/2001
• Status: Active Grant

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: Cytori Therapeutics Incorporated
• Inventors: Fraser, John K., Hedrick, Marc H., Tai, Joseph W., Riley, Susan Lynn
• Granted Patent: US 7,595,043 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61F 2/442 Intervertebral or spinal discs, e.g. resilient non-disc-shaped intervertebral inflatable pockets A61F2/441; non-disc-shaped intervertebral fusion implants A61F2/4455
• CPC Class Codes: A61F 2/4455 for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages intervertebral discs A61F2/442
• CPC Class Codes: A61F 2/4465 having a circular or kidney shaped cross-section substantially perpendicular to the axis of the spine
• CPC Class Codes: A61F 2/447 substantially parallelepipedal, e.g. having a rectangular or trapezoidal cross-section
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30075 swellable, e.g. when wetted
• CPC Class Codes: A61F 2002/30133 kidney-shaped or bean-shaped
• CPC Class Codes: A61F 2002/30448 using adhesives
• CPC Class Codes: A61F 2002/30593 hollow
• CPC Class Codes: A61F 2002/30604 modular
• CPC Class Codes: A61F 2002/30841 Sharp anchoring protrusions for impaction into the bone, e.g. sharp pins, spikes
• CPC Class Codes: A61F 2002/30879 Ribs
• CPC Class Codes: A61F 2002/4445 Means for culturing intervertebral disc tissue
• CPC Class Codes: A61F 2002/445 Intervertebral disc tissue harvest sites
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0061 swellable
• CPC Class Codes: A61F 2220/005 using adhesives
• CPC Class Codes: A61F 2230/0015 Kidney-shaped, e.g. bean-shaped
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 9/0019 : Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: C12N 2506/1384 : from adipose-derived stem cells [ADSC], from adipose stromal stem cells
• CPC Class Codes: C12N 5/0667 : Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/069 : Vascular Endothelial cells

Abstract

The present invention relates to a device comprising a cell carrier portion containing regenerative cells, e.g., stem and progenitor cells, and a cell carrier containment portion. The device is useful for the treatment of bone related disorders, including spinal fusion related disorders and long bone or flat bone related defects. The device may be used in conjunction with disclosed automated systems and methods for separating and concentrating regenerative cells.

Claims

1. A method, comprising:

(1) providing an automated system for separating and concentrating regenerative cells from tissue, the automated system comprising;

a. a chamber assembly to receive tissue removed from a patient, wherein the chamber assembly facilitates disaggregation of the tissue such that regenerative cells are separated from the tissue;

b. a concentrating device which can connect to the chamber assembly, wherein the concentrating device concentrates regenerative cells from the disaggregated tissue present in the chamber assembly; and

c. a programmable processing device capable of communicating with and controlling the chamber assembly and the concentrating device;

(2) providing a device, comprising;

a. a cell carrier portion; and

b. a cell carrier containment portion; and

(3) adding the regenerative cells separated and concentrated by the automated system to the cell carrier portion of the device.

2. The method of claim 1, wherein:

the chamber assembly comprises a collection chamber for facilitating the disaggregation and a processing chamber connected to receive the disaggregated tissue from the collection chamber;

the concentrating device comprises a centrifugation device which can connect to the processing chamber; and

the programmable device is capable of communicating with and controlling both the collection chamber and the processing chamber of the chamber assembly.

3. The method of claim 1, wherein the method is used to treat a bone related disorder.

4. The method of claim 1, wherein the bone related disorder is a spinal fusion defect.

5. The method of claim 1, wherein the bone related disorder is a spinal stabilization defect.

6. The method of claim 1, wherein the bone related disorder is a segmental defect.

7. The method of claim 1, wherein the bone related disorder is in a non-osteoconductive area of the body.

8. The method of claim 1, wherein the bone related disorder is a disorder of the vertebrae.

9. The method of claim 1, wherein the bone related disorder is a disorder of the discs.

10. The method of claim 1, wherein the regenerative cells are comprised of stem cells.

11. The method of claim 1, wherein the regenerative cells are comprised of progenitor cells.

12. The method of claim 1, wherein the regenerative cells are comprised of a combination of stem cells and progenitor cells.

13. The method of claim 1, wherein the cell carrier portion of the device further comprises growth factors.

14. The method of claim 1, wherein the regenerative cells are grown in cell culture prior to placement in the device.

15. The method of claim 14, wherein the regenerative cells are grown in culture conditions that promote differentiation towards a osteogenic phenotype.

16. The method of claim 1, wherein the regenerative cells are autologous cells.

17. The method of claim 1, wherein the device is an interbody spinal fusion device.

18. The method of claim 1, wherein the cell carrier portion and the cell carrier containment portion of the device are in the shape selected from the group consisting of a substantially parabolic shape, a substantially cylindrical shape, a substantially trapezoidal shape and a substantially rectangular shape.

19. The method of claim 1, wherein the cell carrier containment portion is resorbable.

20. The method of claim 19, wherein the cell carrier containment portion is comprised of a polylactide polymer material.

21. The method of claim 20, wherein the polylactide polymer is 70:

30 poly (L-lactide-co-D,L-lactide).

22. The method of claim 1, wherein the cell carrier containment portion is non-resorbable.

23. The method of claim 1, wherein the cell carrier containment portion is comprised of a plurality of apertures.

24. The method of claim 1, wherein the cell carrier portion is porous.

25. The method of claim 1, wherein the cell carrier portion is a gel or a hydrogel.

26. The method of claim 1, wherein the cell carrier portion is resorbable.

27. The method of claim 1, wherein the cell carrier portion is non-resorbable.

28. The method of claim 1, wherein the cell carrier portion is coated with apatite.

29. The method of claim 28, wherein the cell carrier portion is coated using a simulated body fluid solution.

30. The method of claim 1, wherein the tissue is adipose tissue.

31. The method of claim 1, wherein the separated and concentrated regenerative cells are suitable for infusion into a patient.

32. The method of claim 2, wherein the collection chamber of the automated system is further comprised of a filter housed in a filter cage within the collection chamber to retain tissue and filter out non-tissue components selected from the group consisting of free lipid, blood, and a washing solution.

33. The method of claim 2, wherein the collection chamber of the automated system facilitates disaggregation of the tissue through agitation of a rotatable shaft comprised of paddles such that the paddles facilitate disaggregation of the tissue as the rotatable shaft is agitated.

34. The method of claim 33, wherein the paddles are attached to a filter cage within the collection chamber.

35. The method of claim 33, wherein the rotatable shaft is agitated through a magnetic stirrer.

36. The method of claim 2, wherein the collection chamber facilitates disaggregation of the tissue through rotation of a rotatable shaft comprised of paddles such that the paddles facilitate disaggregation of the tissue as the rotatable shaft is rotated.

37. The method of claim 33, wherein the rotatable shaft is rotated through a drive mechanism.

38. The method of claim 1, further comprising a washing solution source.

39. The method of claim 38, wherein the washing solution is saline.

40. The method of claim 1, further comprising a disaggregation agent source.

41. The method of claim 40, wherein the disaggregation agent is selected from the group consisting of collagenase, trypsin, lipase, hyaluronidase, deoxyribonuclease, Liberase H1, pepsin, or mixtures thereof.

42. The method of claim 2, wherein the processing chamber is comprised of one or more centrifuge chambers to hold the disaggregated tissue present in the processing chamber during centrifugation of the disaggregated tissue in the centrifuge device.

43. The method of claim 42, wherein the one or more centrifuge chambers further comprise one or more output chambers to collect the concentrated regenerative cells during centrifugation of the disaggregated tissue in the centrifuge device.

44. The system of claim 43, wherein the one or more output chambers are tilted at a different angle during centrifugation and a different angle for collection of the concentrated regenerative cells.

45. The system of claim 44, wherein the one or more output chamber can be manually re-positioned to arrive at the angle for collection of the concentrated regenerative cells.

46. The system of claim 44, wherein the concentrated regenerative cells are collected using a syringe.

47. The method of claim 2, wherein the processing chamber is comprised of a rotating seal to facilitate collection of the disaggregated tissue in a sterile manner.

48. The method of claim 47, wherein the rotating seal is comprised of a rotating shaft, two or more bearings, three or more lip seals, an outer housing, a circular channel and a circular spring.

49. The method of claim 47, wherein the rotating seal is comprised of a rotating shaft, a single rubber seal, an air gasket, one or more spring loaded seals, and two ceramic disks.

50. The method of claim 2, further comprising a waste chamber.

51. The method of claim 50, wherein the waste chamber receives the non-regenerative cell components of the tissue removed from the patient.

52. The method of claim 51, wherein the non-regenerative cell components present in the waste chamber are centrifuged to separate and concentrate components, including collagen, proteins, lipids, adipocytes and matrix components.

53. The method of claim 2, wherein the collection chamber and the processing chamber are connected through tubing.

54. The system of claim 53, wherein the tubing is further comprised of sensors.

55. The method of claim 2, wherein the collection chamber and the processing chamber further comprise one or more valves, pumps, sensors or combinations thereof.

56. The system of claim 54, wherein the collection chamber, the processing chamber and the tubing are disposable.

57. They method of claim 2, wherein the centrifuge device and the processing device are re-usable.

58. The method of claim 2, wherein the centrifugation device further comprises a centrifuge motor, a centrifuge motor controller and a centrifuge brake controller.

59. The method of claim 2, wherein the processing device controls the collection chamber, the processing chamber and the centrifuge chamber by directing tissue flow through the use of one or more pumps.

60. The method of claim 59, wherein the pumps are peristaltic pumps.

61. The method of claim 59, wherein the pumps are re-usable.

62. The method of claim 1, wherein the processing device further comprises a user interface for a user to input parameters into the system.

63. The method of claim 1, wherein the processing device further comprises a display screen to display instructions that guide a user to input parameters, confirm pre-programmed steps, warn of errors or combinations thereof.

64. The method of claim 1, wherein one or more additives are added to the regenerative cells before the cells are added to the device.

65. The method of claim 64, wherein the additives are selected from growth factors, re-suspension fluids, cell culture reagents, cell expansion reagents, cell preservation reagents or cell modification reagents, or combinations thereof.

66. The method of claim 1, wherein one or more additives are added to the regenerative cells after the cells are added to the device.

67. The method of claim 66, wherein the additives are selected from growth factors, re-suspension fluids, cell culture reagents, cell expansion reagents, cell preservation reagents or cell modification reagents, or combinations thereof.

68. A method of promoting bone or cartilage formation in a patient, comprising:

a) providing a tissue removal system and a device comprising a cell carrier portion and a cell carrier containment portion, which is constructed to at least partially contain the cell carrier portion;

b) removing adipose tissue from the patient using the tissue removal system;

c) processing at least a part of the adipose tissue to obtain a concentration of regenerative cells;

d) adding the regenerative cells to the cell carrier portion of the device; and

e) inserting the device into the intended bone formation area in the patient to thereby promote at least one of bone and cartilage formation in the patient.

69. The method of claim 68, wherein bone and cartilage formation are promoted in the patient.

70. The method of claim 68, wherein the providing of a device comprises providing the cell carrier containment portion with a center hole for insertion of the cell carrier portion.

71. The method of claim 70, wherein the providing of a device comprises:

providing the cell carrier portion, which comprises a parabolic shape and which is porous; and

providing the cell carrier containment portion, which comprises a parabolic shape.

72. A method of promoting bone or cartilage formation in a patient comprising:

a) providing a tissue removal system and a device comprising a cell carrier portion and a cell carrier containment portion, which is configured to at least partially contain the cell carrier portion;

b) removing adipose tissue from the patient using the tissue removal system;

c) processing at least a part of the adipose tissue to obtain a concentration of regenerative cells;

d) inserting the device into the intended bone formation area in the patient;

e) adding the regenerative cells to the cell carrier portion of the device inserted into the patient to thereby promote at least one of bone and cartilage formation in the patient.

73. The method of claim 72, wherein the adding of the regenerative cells promotes bone and cartilage formation in the patient.

74. The method of claim 72, wherein the providing of a device comprises providing the cell carrier containment portion with a center hole for insertion of the cell carrier portion.

75. The method of claim 74, wherein the providing of a device comprises:

providing the cell carrier portion, which comprises a parabolic shape and which is porous; and

providing the cell carrier containment portion, which comprises a parabolic shape.

76. The method of claim 72, wherein:

the processing of at least a part of the adipose tissue comprises processing at least a part of the adipose tissue to obtain a therapeutically effective dose of regenerative cells; and

the adding of the regenerative cells comprises adding the therapeutically effective dose of regenerative cells to the cell carrier portion of the device inserted into the patient to thereby promote at least one of bone and cartilage formation in the patient.

77. The method of claim 76, wherein the adding of the therapeutically effective dose of regenerative cells promotes bone and cartilage formation in the patient.