Systems and methods for treating patients with processed lipoaspirate cells

• US 20070036768A1
• Filed: 10/20/2006
• Published: 02/15/2007
• Est. Priority Date: 12/07/2001
• Status: Active Grant

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: John Fraser, Marc Hedrick
• Inventors: Fraser, John, Hedrick, Marc
• Granted Patent: US 7,687,059 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61B 10/0283 with vacuum aspiration, e.g. caused by retractable plunger or by connected syringe A61B10/025, A61B10/0266 take precedence
• 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 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• 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: A61M 1/76 Handpieces specially for suction-irrigation A61M1/774, aspiration tips A61M1/84
• CPC Class Codes: A61M 2202/08 Lipoids
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• 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: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12M 47/04 : Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04
• 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

Cells present in processed lipoaspirate tissue are used to treat patients. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of stem 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. Compositions that are administered to a patient include a mixture of adipose tissue and stem cells so that the composition has a higher concentration of stem cells than when the adipose tissue was removed from the patient.

Claims

1. A self contained adipose-derived stem cell processing unit, comprising:

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

a first filter that is disposed within said tissue collection container, which is configured to retain adipose tissue and pass lipid, blood, and saline;

a cell collection chamber, which is configured to receive and concentrate a population of cells that comprises adipose-derived stem cells from said tissue collection container, wherein said cell collection container is within said closed system; and

an outlet configured to allow the aseptic removal of said concentrated population of cells that comprise adipose-derived stem cells.

2. A method of using the self-contained adipose-derived stem cell processing unit of claim 1 to process a cell population that comprises adipose stem cells for reintroduction into a patient, comprising:

removing a first portion of adipose tissue that comprises adipose-derived stem cells from said patient;

introducing the removed first portion of adipose tissue into the adipose-derived stem cell processing unit of claim 1;

separating said cell population that comprises adipose-derived stem cells from mature adipocytes and connective tissue present in the first portion of adipose tissue that was removed from said patient such that said mature adipocytes and said connective tissue are substantially separated from said cell population that comprises adipose-derived stem cells within said self-contained cell processing unit while maintaining said closed pathway;

concentrating said cell population that comprises adipose-derived stem cells with said self-contained cell processing unit while maintaining said closed pathway; and

reintroducing said concentrated cell population that comprises adipose-derived stem cells into said patient.

3. The method of claim 2, further comprising providing said patient or said concentrated cell population that comprises adipose-derived stem cells an additive.

4. The method of claim 2, further comprising mixing said concentrated cell population that comprises adipose-derived stem cells with a second portion of adipose tissue from said patient within said self-contained processing unit while maintaining said closed pathway, and reintroducing said mixture of said concentrated cell population that comprises adipose-derived stem cells and said second portion of adipose tissue into said patient.

5. The method of claim 2, further comprising cooling said concentrated cell population that comprises adipose-derived stem cells, while maintaining a closed pathway.

6. The method of claim 2, wherein said concentrated cell population that comprises adipose derived stem cells is reintroduced into said patient while maintaining a closed pathway.

7. The method of claim 2, wherein said first portion of adipose tissue that is removed from said patient is lipoaspirate.

8. The method of claim 2, wherein said first portion of adipose tissue that is removed from said patient is obtained by excisional lipectomy.

9. The method of claim 4, wherein said second portion of adipose tissue that is removed from said patient is lipoaspirate.

10. The method of claim 4, wherein said second portion of adipose tissue that is removed from said patient is obtained by excisional lipectomy.

11. The method of claim 2, wherein said concentrated cell population comprising adipose-derived stem cells is reintroduced into said patient subcutaneously, intravenously, intramuscularly, or intraperitoneally.

12. The method of claim 3, wherein said additive is a tissue. or tissue fragment.

13. The method of claim 3, wherein said additive is demineralized bone.

14. The method of claim 3, wherein said additive is a compound of the thiaglitazone family.

15. The method of claim 3, wherein said additive is insulin.

16. The method of claim 3, wherein said additive is an exogenous DNA.

17. The method of claim 3, wherein said additive is a biological or artificial scaffold.

18. The method of claim 17, wherein said biological or artificial scafflold is a resorbable plastic sheath.

19. The method of claim 3, wherein said additive is an immunosuppressive agent.

20. The method of claim 19, wherein said immunosuppressive agent is selected from the group consisting of cyclosporine, myophenylate mofetil, rapamycin, and antithymocyte globulin.

21. The method of claim 3, wherein said additive is a cell differentiation agent.

22. The method of claim 21, wherein said cell differentiation agent is a cytokine.

23. The method of claim 21, wherein said cell differentiation agent is a growth factor.

24. The method of claim 3, wherein said additive is an antimicrobial agent.

25. The method of claim 3, wherein said patient is provided said additive.

26. The method of claim 3, wherein said concentrated cell population that comprises adipose derived stem cells is provided said additive.

27. The method of claim 2, further comprising a disaggregation step, wherein said cell population comprising adipose-derived stem cells contained in the removed adipose tissue is mechanically or enzymatically disaggregated from said mature adipocytes and connective tissue present in the adipose tissue that was removed from said patient prior to separation.

28. The method of claim 2, wherein said cell population comprising said adipose-derived stem cells is separated from said mature adipocytes and connective tissue present in the first portion of adipose tissue that was removed from said patient by employing a filter.

29. The method of claim 28, wherein said filter is a spinning membrane filter.

30. The method of claim 28, wherein said filter comprises an antibody.

31. The method of claim 30, wherein said antibody is selected from the group consisting of AP2, CD3, CD19, and CD11b.

32. The method of claim 2, wherein said cell population comprising said adipose-derived stem cells is separated from said mature adipocytes and connective tissue present in the first portion of adipose tissue that was removed from said patient by centrifugation.

33. The method of claim 27, wherein said disaggregation step comprises an enzymatic digestion.

34. The method of claim 33, wherein said enzymatic digestion comprises a collagenase.

35. The method of claim 33, wherein said enzymatic digestion comprises a neutral protease.

36. The method of claim 33, wherein said enzymatic digestion comprises trypsin.

37. The method of claim 2, wherein said concentrated cell population that comprises adipose-derived stem cells comprises endothelial precursor cells.

38. The method of claim 2, wherein said patient has a disease or injury selected from the group consisting of slow/non-union fractures, osteoporosis, osteogenesis imperfecta, liver failure, hepatitis B, hepatitis C, myocardial infarction, renal disease, retinal disease, ulcers, muscle disorders, cartilage disorder, lung disease, diabetes, intestinal disorder, central nervous system disorder, spinal cord injury, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, chronic heart disease, and stroke.

39. The method of claim 2, wherein said patient has wrinkles, divots, or pockmarks.

40. The method of claim 2, wherein said patient has liver injury.

41. The method of claim 40, further comprising measuring liver regeneration.

42. The method of claim 5, further comprising removing a portion of said cooled, concentrated cell population that comprises adipose-derived stem cells from said self-contained cell processing unit.

43. The method of claim 42, wherein said cooled, concentrated cell population that comprises adipose-derived stem cells that is removed from said self-contained cell processing unit is cryopreserved.

44. A composition comprising a concentrated cell population comprising adipose-derived stem cells obtainable by the self-contained adipose-derived stem cell processing unit of claim 1, wherein said adipose-derived stem cells comprise at least about 0.1% of the cellular component.

45. The composition of claim 44, wherein said adipose-derived stem cells comprise between about 2% and about 12% adipose-derived stem cells.

46. The composition of claim 44, wherein said concentrated cell population that comprises adipose-derived stem cells has a concentration of about 2×

10⁷ cells/100 ml adipose tissue.

47. The composition of claim 44, further comprising a portion of unprocessed adipose tissue, wherein said concentrated cell population and said portion of unprocessed adipose tissue comprise a mixture, and wherein the volume of said portion of unprocessed adipose tissue is at least 25% greater than the volume of said concentrated cell population of said mixture.

48. The composition of claim 47, wherein the volume of said portion of unprocessed adipose tissue of said mixture is at least 50% greater than the volume of said concentrated cell population of said mixture.

49. The composition of claim 48, wherein the volume of said portion of unprocessed adipose tissue of said mixture is at least 100% greater than the volume of said concentrated cell population of said mixture.

50. The composition of claim 49, wherein the volume of said portion of unprocessed adipose tissue of said mixture is at least 150% greater than the volume of said concentrated cell population of said mixture.

51. The composition of claim 44, wherein the concentrated cell population comprising adipose-derived stem cells is cryopreserved material.

52. The composition of claim 47, wherein the second portion of adipose tissue of said mixture is cryopreserved material.

53. The composition of claim 44, further comprising an additive.

54. The composition of claim 55, wherein said additive is a tissue or tissue fragment.

55. The composition of claim 53, wherein said additive is demineralized bone.

56. The composition of claim 53, wherein said additive is a compound of the thiaglitazone family.

57. The composition of claim 53, wherein said additive is insulin.

58. The composition of claim 53, wherein said additive is an exogenous DNA.

59. The composition of claim 53, wherein said additive is a biological or artificial scaffold.

60. The composition of claim 60, wherein said biological or artificial scaffold is a resorbable plastic sheath.

61. The composition of claim 53, wherein said additive is an immunosuppressive agent.

62. The composition of claim 61, wherein said immunosuppressive agent is selected from the group consisting of cyclosporine, myophenylate mofetil, rapamycin, and antithymocyte globulin.

63. The composition of claim 53, wherein said additive is a cell differentiation agent.

64. The composition of claim 63, wherein said cell differentiation agent is a cytokine.

65. The method of claim 63, wherein said cell differentiation agent is a growth factor.

66. The composition of claim 53, wherein said additive is an antimicrobial agent.

67. The composition of claim 44, wherein said concentrated cell population that comprises adipose-derived stem cells comprises endothelial precursor cells.