Method for processing and using adipose-derived stem cells

• US 7,595,043 B2
• Filed: 07/01/2004
• Issued: 09/29/2009
• 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
• Primary Examiner(s): LANKFORD JR, LEON B
• Application Number:
  US10/885,293
• Publication Number:
  US 20050058632A1
• Time in Patent Office: 1,916 Days
• Field of Search: None
• US Class Current: 424/93.7
• 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 of processing adipose tissue that comprises a population of cells comprising adipose-derived stem cells for reintroduction into a patient, comprising:

removing unprocessed adipose tissue that comprises a cell population comprising adipose-derived stem cells from said patient;

introducing the removed adipose tissue into a self contained adipose-derived stem cell processing unit configured to maintain a closed system wherein said self contained adipose-derived stem cell processing unit comprises

a tissue collection chamber that is configured to receive unprocessed adipose tissue that is removed from said patient, wherein the tissue collection chamber is defined by a closed system;

a first filter that is disposed within said tissue collection chamber, wherein said first filter is configured to retain a first component of said unprocessed adipose tissue and pass a second component of said unprocessed adipose tissue, such that said first filter separates said first component from said second component, and wherein said first component comprises a cell population comprising adipose-derived stem cells and said second component comprises lipid, mature adipocytes, and saline;

a processing chamber, which is configured to receive said first component comprising said population of cells comprising adipose-derived stem cells from said tissue collection chamber, wherein said processing chamber is within said closed system;

a conduit configured to allow passage of said first component comprising said cell population comprising adipose-derived stem cells from said tissue collection chamber to said processing chamber while maintaining a closed system;

a cell concentrator disposed within said processing chamber, which is configured to facilitate the concentration of said first component comprising said cell population comprising adipose-derived stem cells so as to obtain a concentrated population of cells comprising adipose-derived stem cells, wherein said cell concentrator comprises a centrifuge or a filter; and

an outlet configured to allow the aseptic removal of said concentrated population of cells comprising adipose-derived stem cells;

processing said removed, unprocessed adipose tissue to obtain said concentrated population cell comprising adipose-derived stem cells; and

introducing said concentrated population of cells that comprises adipose-derived stem cells into a prosthetic device, wherein said prosthetic device comprises a cell carrier portion and a cell carrier containment portion, and wherein said concentrated population of cells comprising adipose-derived stem cells is introduced into said cell carrier portion of said prosthetic device.

2. The method of claim 1, wherein said chamber tissue collection chamber is configured to facilitate disaggregation of said removed adipose tissue;

wherein said processing chamber receives the disaggregated tissue from the collection chamber;

wherein said cell concentrator comprises a centrifuge; and

wherein said processing step comprises disaggregation of said adipose tissue that comprises a cell population that comprises adipose-derived stem cells so as to obtain a disaggregated cell population that comprises adipose-derived stem cells, and centrifugation of said disaggregated cell population that comprises adipose-derived stem cells.

3. The method of claim 1, wherein said patient has a bone related disorder.

4. The method of claim 3, wherein the bone related disorder is a spinal fusion defect.

5. The method of claim 3, wherein the bone related disorder is a spinal stabilization defect.

6. The method of claim 3, wherein the bone related disorder is a segmental defect.

7. The method of claim 3, wherein the bone related disorder is in a non-osteoconductive area of the body.

8. The method of claim 3, wherein the bone related disorder is a disorder of the vertebrae.

9. The method of claim 3, wherein the bone related disorder is a disorder of the discs.

10. The method of claim 1, wherein said concentrated population cells further comprises progenitor cells.

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

12. The method of claim 1, further comprising culturing said concentrated population of cells comprising adipose-derived stem cells prior to introducing said concentrated population of cells comprising adipose-derived stem cells into said prosthetic device.

13. The method of claim 12, wherein said culturing step comprises exposing the concentrated population of cells comprising adipose-derived stem cells to culture conditions that promote differentiation towards a osteogenic phenotype.

14. The method of claim 1, wherein the concentrated population of cells comprising adipose-derived stem cells are autologous cells.

15. The method of claim 1, wherein said prosthetic device is an interbody spinal fusion device.

16. The method of claim 1, wherein the cell carrier portion and the cell carrier containment portion of said prosthetic 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.

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

18. The method of claim 17, wherein the cell carrier containment portion comprises a polylactide polymer material.

19. The method of claim 18, wherein the polylactide polymer is 70:

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

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

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

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

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

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

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

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

27. The method of claim 26, wherein the cell carrier portion is coated using a simulated body fluid solution.

28. The method of claim 1, wherein said concentrated population of cells comprising adipose-derived stem cells is suitable for infusion into a patient.

29. The method of claim 2, wherein said first filter is housed in a filter cage within the tissue collection chamber.

30. The method of claim 1, wherein said self contained adipose-derived stem cell processing unit further comprises a washing solution source.

31. The method of claim 30, wherein the washing solution is saline.

32. The method of claim 1, wherein said self-contained adipose-derived stem cell processing unit further comprises a disaggregation agent source.

33. The method of claim 32, wherein the disaggregation agent is selected from the group consisting of collagenase, trypsin, lipase, hyaluronidase, deoxyribonuclease, Liberase H1, pepsin, or mixtures thereof

34. The method of claim 2, wherein the processing chamber comprises one or more centrifuge chambers, wherein said one or more centrifuge chambers are configured to hold the disaggregated adipose tissue present in the processing chamber during centrifugation of the disaggregated tissue in the centrifuge device.

35. The method of claim 34, wherein the one or more centrifuge chambers further comprise one or more output chambers, wherein said one or more output chambers are configured to collect the concentrated population of cells comprising adipose-derived stem cells during centrifugation of the disaggregated tissue in the centrifuge device.

36. The method of claim 35, wherein the one or more output chambers are tilted at a first angle during centrifugation and a second angle for collection of the concentrated population of cells comprising adipose-derived stem cells.

37. The method of claim 36, wherein the one or more output chambers is configured to manually re-position the angle of said output chamber.

38. The method of claim 36, further comprising collecting said concentrated population of cells comprising adipose-derived stem cells a syringe.

39. The method of claim 2, wherein the processing chamber comprises a rotating seal configured to facilitate collection of the disaggregated tissue in a sterile manner.

40. The method of claim 39, 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.

41. The method of claim 39, 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.

42. The method of claim 2, wherein said self contained adipose-derived stem cell processing unit further comprises a waste chamber,

43. The method of claim 42, wherein the waste chamber is configured to receive the non-stem cell components of the adipose tissue removed from the patient.

44. The method of claim 43, further comprising centrifuging the non-stem cell components present in the waste chamber to separate and concentrate collagen, proteins, lipids, adipocytes and matrix components.

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

46. The system of claim 45, wherein the tubing further comprises one or more sensors.

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

48. The method of claim 46, wherein the tissue collection chamber, the processing chamber and the tubing are disposable.

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

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

51. 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.

52. The method of claim 51, wherein the pumps are peristaltic pumps.

53. The method of claim 51, wherein the pumps are re-usable.

54. The method of claim 1, further comprising adding one or more additives to the concentrated population of cells comprising adipose-derived stem cells before introducing the concentrated population of cells comprising adipose-derived stem cells into the prosthetic device.

55. The method of claim 54, 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

56. The method of claim 1, further comprising adding one or more additives to the concentrated population of cells comprising adipose-derived stem cells after introducing the concentrated population of cells comprising adipose-derived stem cells into the prosthetic device.

57. The method of claim 56, wherein the additives are selected from the group consisting of growth factors, re-suspension fluids, cell culture reagents, cell expansion reagents, cell preservation reagents and cell modification reagents, or combinations thereof.

68. The method of claim 1, wherein the self contained adipose-derived stem cell processing unit further comprises a programmable processing device capable of communicating with and controlling the tissue collection chamber and the cell concentrator.

69. The method of claim 68, wherein the self contained adipose-derived stem cell processing unit further comprises a user interface for a user to input parameters into the system.

70. The method of claim 68, wherein the self contained adipose-derived stem cell processing unit further comprises a display screen to display instructions that guide a user to input parameters, confirm pre-programmed steps, or warn of errors or combinations thereof

71. The method of claim 1, wherein the tissue collection chamber is configured to be agitated or rotated to an arc of about 40 degrees to about 90 degrees.

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

a) providing a tissue removal system and a prosthetic device comprising a cell carrier portion and a cell carrier containment portion, said cell carrier containment portion being 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 concentrated population of cells comprising adipose-derived stem cells;

d) introducing the concentrated population of cells comprising adipose-derived stem cells to the cell carrier portion of the prosthetic device; and

e) inserting the prosthetic device containing the concentrated population of cells comprising adipose-derived stem cells into the intended bone formation area in the patient.

59. The method of claim 58, wherein bone and cartilage formation are promoted in the patient.

60. The method of claim 58, wherein the cell carrier containment portion of said prosthetic device comprises a center hole for insertion of the cell carrier portion.

61. The method of claim 60, wherein the carrier portion comprises a parabolic shape and is porous;

and wherein the cell carrier containment portion comprises a parabolic shape.

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

a) providing a self contained adipose derived stem cell processing unit and a device comprising a cell carrier portion and a cell carrier containment portion, wherein said cell carrier containment portion is configured to at least partially contain the cell carrier portion, wherein said self contained adipose derived stem cell processing unit comprises

a tissue collection chamber that is configured to receive unprocessed adipose tissue that is removed from said patient, wherein the tissue collection chamber is defined by a closed system;

a first filter that is disposed within said tissue collection chamber, wherein said first filter is configured to retain a first component of said unprocessed adipose tissue and pass a second component of said unprocessed adipose tissue, such that said first filter separates said first component from said second component, and wherein said first component comprises a cell population comprising adipose-derived stem cells and said second component comprises lipid, mature adipocytes, and saline;

a processing chamber, which is configured to receive said first component comprising said population of cells comprising adipose-derived stem cells from said tissue collection chamber, wherein said processing chamber is within said closed system;

a conduit configured to allow passage of said first component comprising said cell population comprising adipose-derived stem cells from said tissue collection chamber to said processing chamber while maintaining a closed system;

a cell concentrator disposed within said processing chamber, which is configured to facilitate the concentration of said first component comprising said cell population comprising adipose-derived stem cells so as to obtain a concentrated population of cells comprising adipose-derived stem cells, wherein said cell concentrator comprises a centrifuge or a filter; and

an outlet configured to allow the aseptic removal of said concentrated population of cells comprising adipose-derived stem cells;

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 concentrated population of cells comprising adipose-derived stem cells;

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

e) introducing the regenerative cells to the cell carrier portion of the device inserted into the patient.

63. The method of claim 62, wherein introducing the concentrated population of cell comprising adipose-derived stem cells to said cell carrier portion of the device inserted into the patient promotes bone and cartilage formation in the patient.

64. The method of claim 62, wherein the cell carrier containment portion of said device comprises a center hole configured to receive the cell carrier portion of said device.

65. The method of claim 64, wherein the providing of a device comprises-carrier portion comprises a parabolic shape and is porous;

and wherein the cell carrier containment portion comprises a parabolic shape.

66. The method of claim 62, wherein the processing step comprises processing at least a part of the adipose tissue to obtain a therapeutically effective amount of adipose-derived stem cells;

and

the introducing step comprises adding the therapeutically effective amount of adipose-derived stem cells to the cell carrier portion of the prosthetic device inserted into the patient.

67. The method of claim 66, wherein the introducing of the therapeutically effective amount of adipose-derived stem cells to the cell carrier portion of the device promotes bone and cartilage formation in the patient.