Methods of using regenerative cells in the treatment of musculoskeletal disorders

• US 20050048644A1
• Filed: 07/01/2004
• Published: 03/03/2005
• 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., Schreiber, Ronda Elizabeth, Riley, Susan Lynn
• Granted Patent: US 7,771,716 B2
• Time in Patent Office: Days
• US Class Current: 435/289.100
• 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: A61L 2300/40 characterised by a specific therapeutic activity or mode of action
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/3654 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• 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 27/3847 Bones
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C12N 5/0667 : Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

Regenerative cells present in adipose tissue are used to treat patients, including patients with musculoskeletal diseases or disorders. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of regenerative cells obtained from the adipose tissue to a patient. The methods may be practiced in a closed system so that the stem cells are not exposed to an external environment prior to being administered to a patient. Accordingly, in a preferred method, regenerative cells present in adipose tissue are placed directly into a recipient along with such additives necessary to promote, engender or support a therapeutic musculoskeletal benefit.

Claims

1. A method for inducing bone, cartilage, skeletal muscle, tendon, ligament or proteoglycan-rich matrix formation comprising

(1) providing a programmable, automated system for concentrating regenerative cells from tissue;

and

(2) placing the concentrated regenerative cells in a patient to induce bone, cartilage, skeletal muscle, tendon, ligament or proteoglycan-rich matrix formation.

2. The method of claim 1, wherein the providing comprises providing an 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 concentration device which can be connected to concentrate regenerative cells from the chamber assembly; and

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

3. The method of claim 2, wherein the concentration device comprises a centrifugation device.

4. The method of claim 3, wherein the chamber assembly comprises a collection chamber and a processing chamber.

5. The method of claim 4, wherein:

the providing comprises coupling the processing chamber to the collection chamber; and

the centrifugation device is configured to connect with and receive the disaggregated tissue from the collection chamber.

6. The method of claim 2, wherein the tissue is adipose tissue.

7. The method of claim 2, wherein the regenerative cells are stem cells.

8. The method of claim 2, wherein the regenerative cells are progenitor cells.

9. The method of claim 2, wherein the regenerative cells are a combination of stem cells and progenitor cells.

10. The method of claim 2, wherein the separated and concentrated regenerative cells are suitable for infusion into a patient.

11. The method of claim 10, wherein the regenerative cells are used to treat a patient.

12. The method of claim 2, wherein the regenerative cells are used to repair an intervertebral disc.

13. The method of claim 12, wherein the intervertebral disc is repaired by production of a preoteoglycan rich matrix.

14. The method of claim 12, wherein the regenerative cells are placed into a patient through direct injection into the intervertebral disc.

15. The method of claim 12, wherein the regenerative cells are placed into a patient through injection into a settable hydrogel.

16. The method of claim 2, wherein the regenerative cells are used to induce bone formation for intervertebral body spinal fusion.

17. The method of claim 2, wherein the regenerative cells are used to induce bone formation for intertransverse process spinal fusion.

18. The method of claim 2, wherein the regenerative cells are used to induce cartilage formation.

19. The method of claim 2, wherein the cartilage formation is at the end of long bones.

20. The method of claim 2, wherein the cartilage formation is in the knee joint.

21. The method of claim 2, wherein the cartilage formation is in the ribs.

22. The method of claim 18, wherein the regenerative cells are placed into a patient through direct injection into the site of cartilage formation.

23. The method of claim 18, wherein the regenerative cells are placed into a site of cartilage formation through injection into a settable hydrogel.

24. The method of claim 2, wherein the regenerative cells are used to induce bone formation for repairing long bone fractures.

25. The method of claim 2, wherein the regenerative cells are used to induce bone and cartilage formation.

26. The method of claim 25, wherein the regenerative cells are used to repair a tendon.

27. The method of claim 26 wherein the tendon is at the tendon-bone insertion site.

28. The method of claim 2, wherein the regenerative cells are used to induce skeletal muscle formation.

29. The method of claim 28, wherein the skeletal muscle formation is used for tendon repair at the tendon-muscle insertion site.

30. The method of claim 28, wherein the skeletal muscle formation is used for ligament repair at the ligament-muscle insertion site.

31. The method of claim 28, wherein the skeletal muscle formation is used for ligament repair at the ligament-bone insertion site.

32. The method of claim 2, wherein the regenerative cells are used to induce formation of tendon.

33. The method of claim 2, wherein the regenerative cells are used to induce formation of ligament.

34. The method of claim 4, 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.

35. The method of claim 4, 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.

36. The method of claim 35, wherein the paddles are attached to a filter cage within the collection chamber.

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

38. The method of claim 2, wherein the collection chamber of the automated system 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 as the rotatable shaft is rotated.

39. The method of claim 35, wherein the rotatable shaft is rotated through a drive mechanism.

40. The method of claim 4, wherein the automated system is further comprised of a washing solution source.

41. The method of claim 40, wherein the washing solution is saline.

42. The method of claim 4, wherein the automated system is further comprised of a disaggregation agent source.

43. The method of claim 42, wherein the disaggregation agent is selected from the group consisting of collagenase, trypsin, lipase, hyaluronidase, deoxyribonuclease, Liberase HI, pepsin, or mixtures thereof.

44. The method of claim 5, wherein the processing chamber of the automated system 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.

45. The method of claim 44, 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.

46. The method of claim 45, 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.

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

48. The method of claim 47, wherein the concentrated regenerative cells are removed using a syringe.

49. The method of claim 4, wherein the processing chamber of the automated system is comprised of a rotating seal to facilitate collection of the disaggregated tissue in a sterile manner.

50. The method of claim 49, 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.

51. The method of claim 49, 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.

52. The method of claim 2, wherein the automated system is further comprised of a waste chamber.

53. The method of claim 52, wherein the waste chamber receives the non-regenerative cell components of the tissue removed from the patient.

54. The method of claim 53, 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.

55. The method of claim 53, wherein the non-regenerative cell components present in the waste chamber are filtered to separate and concentrate components, including collagen, proteins, lipids, adipocytes and matrix components.

56. The method of claim 5, wherein the collection chamber and the processing chamber of the automated system are connected through tubing.

57. The method of claim 56, wherein the tubing is further comprised of sensors.

58. The method of claim 5, wherein the collection chamber and the processing chamber of the automated system further comprise one or more valves, pumps, sensors or combinations thereof.

59. The method of claim 56, wherein the collection chamber, the processing chamber and the tubing are disposable.

60. They method of claim 5, wherein the centrifuge device and the processing device of the automated system are re-usable.

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

62. The method of claim 5, wherein the processing device of the automated system controls the centrifuge chamber, the processing chamber and the centrifuge chamber by directing tissue flow through the use of one or more pumps.

63. The method of claim 62, wherein the pumps are peristaltic pumps.

64. The method of claim 63, wherein the pumps are re-usable.

65. The method of claim 2, wherein the processing device further comprises a user interface for a user to input parameters into the system.

66. The method of claim 2, 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.

67. The method of claim 2, wherein a portion of the tissue removed from the patient is used to separate and concentrate regenerative cells and the remaining portion is set aside.

68. The method of claim 67, wherein the remaining portion of tissue is set aside in a sample chamber.

69. The method of claim 2, wherein one or more additives are added to the regenerative cells.

70. The system of claim 69, 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.

71. The method of claim 2, wherein regenerative cells are grown in cell culture prior to placement in the device.

72. The method of claim 71, wherein the regenerative cells are grown in culture conditions that promote differentiation towards a osteogenic phenotype.

73. The method of claim 2, wherein the regenerative cells are placed on a surgical device or implant prior to being placed into a patient.

74. The method of claim 73, wherein the surgical device is a spinal fusion device.

75. The method of claim 73, wherein the surgical implant is a scaffold.

76. The method of claim 75, wherein the scaffold is porous.

77. The method of claim 2, wherein the regenerative cells are placed in a gel or a hydrogel prior to being placed into a patient.

78. The method of claim 2, further comprising a second system wherein the second system is connected to the first system.

79. The method of claim 78, wherein the second system cultures the regenerative cells.

80. The method of claim 78, wherein the second system genetically manipulates the regenerative cells.

81. A method for contacting matter with regenerative cells, comprising:

(1) automatically separating regenerative cells from tissue received into a first system and concentrating the regenerative cells from the tissue using a second system, the first and second systems operating automatically under control of a controller which is programmable to automatically perform a plurality of coordinated separating and concentrating procedures using the first and second systems; and

(2) placing the concentrated regenerative cells into contact with matter to induce a predetermined effect.

82. The method of claim 81, wherein the matter comprises at least one of bone, cartilage, skeletal muscle, tendon and ligament.

83. The method of claim 82, wherein the predetermined effect comprises an induced formation of at least one of bone, cartilage, skeletal muscle, tendon and ligament.

84. The method of claim 83, wherein the separating of regenerative cells from tissue comprises at least partially disaggregating regenerative cells from tissue removed from a patient and the concentrating of the regenerative cells comprises centrifuging the regenerative cells.