Embryonic-like stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells

• US 20030180269A1
• Filed: 02/13/2003
• Published: 09/25/2003
• Est. Priority Date: 02/13/2002
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Hariri, Robert J.
• Granted Patent: US 7,311,905 B2
• Time in Patent Office: Days
• US Class Current: 424/93.21
• 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 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61M 1/02 Blood transfusion apparatus blood infusion by syringes A61M5/14
• CPC Class Codes: A61M 2202/0462 Placental blood, umbilical cord blood
• CPC Class Codes: A61M 2210/1458 Placenta
• CPC Class Codes: A61M 2210/1466 Umbilical cord
• 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 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 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 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: C12N 2500/90 : Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 2509/00 : Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2533/90 : Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0607 : Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The present invention provides compositions and methods of using embryonic-like stem cells that originate from a post-partum placenta with conventional cord blood compositions or other stem or progenitor cells. The embryonic-like stem cells can be used alone or in a mixture with other stem cell populations. In accordance with the present invention, the embryonic-like stem cells may be mixed with other stem cell populations, including but not limited to, umbilical cord blood, fetal and neonatal hematopoietic stem cells and progenitor cells, human stem cells and progenitor cells derived from bone marrow. The embryonic-like stem cells and the mixed populations of embryonic-like stem cells and stem cells have a multitude of uses and applications, including but not limited to, therapeutic uses for transplantation and treatment and prevention of disease, and diagnostic and research uses.

Claims

1. A composition comprising stem or progenitor cells and embryonic-like stem cells.

3. The composition of claim 1 that comprises a population of stem or progenitor cells and a population of embryonic-like stem cells.

4. The composition of claim 1 or 2 that is contained in a container.

5. The composition of claim 4 wherein the container is sealed, air tight, and sterile.

6. The composition of claim 1 or 2 wherein the stem or progenitor cells and embryonic-like stem cells are in contact with each other prior to or at the time of administration to a patient in need thereof.

7. The composition of claim 1 or 2 wherein stem or progenitor cells and embryonic-like stem cells are suitable for administration separately to a patient.

8. The composition of claim 1 or 2 that is suitable for bone marrow transplantation.

9. The composition of claim 1 or 2 that is suitable for administration in humans.

10. The composition of claim 1 or 2 wherein the stem or progenitor cells are from umbilical cord blood or placental blood, fetal or neonatal hematopoietic stem or progenitor cells, human stem cells, adult cells or bone marrow stem or progenitor cells.

11. The composition of claim 10 wherein the stem or progenitor cells are fetal or neonatal hematopoietic stem or progenitor cells.

12. The composition of claim 11 wherein a plurality of the hematopoietic stem or progenitor cells express the cell surface markers CD34+ and CD38−

.

13. The composition of claim 10 wherein the stem or progenitor cells are umbilical cord blood stem cells.

14. The composition of claim 13 wherein a plurality of the umbilical cord blood stem cells express the cell surface markers CD34+ and CD38−

.

15. The composition of claim 13 wherein a plurality of the umbilical cord blood stem cells express the cell surface markers CD34+ and CD38+.

16. The composition of claim 1 or 2 wherein the embryonic-like stem cells exhibit at least one of the following cell surface markers:

CD10, CD29, CD44, CD54, CD90, SH2, SH3, SH4, OCT-4 or ABC-p, or lacks at least one of the following cell surface markers;

CD34, CD45, SSEA3, SSEA4.

17. The composition of claim 16 wherein the embryonic-like stem cells are OCT-4+ and ABC-p+.

18. The composition of claim 16 wherein the embryonic-like stem cells are SSEA3−

and SSEA4−

.

19. A kit comprising a composition of claim 1 or 2 wherein said stem or progenitor cells are in a first container and said embryonic-like stem cells are in a second container.

2. A composition comprising umbilical cord blood cells and embryonic-like stem cells.

20. A method of treating a patient in need thereof comprising administration of a plurality of umbilical cord blood cells and a plurality of embryonic-like stem cells.

21. A method of treating a patient in need thereof comprising administration of a plurality of umbilical cord blood cells and a plurality of embryonic-like stem cells.

22. The method of claim 21 wherein the plurality of umbilical cord blood cells and the plurality of embryonic-like stem cells is each contained in a separate container prior to mixing.

23. The method of claim 21 wherein the plurality of umbilical cord blood cells and the plurality of embryonic-like stem cells are in contact with each other prior to or at the time of administration to a patient in need thereof.

24. The method of claim 21 wherein the plurality of umbilical cord blood cells and the plurality of embryonic-like stem cells are suitable for administration separately to a patient.

25. The method of claim 21 wherein the umbilical cord blood cells are fetal or neonatal hematopoietic stem or progenitor cells.

26. The method of claim 25 wherein a plurality of the hematopoietic stem or progenitor cells express the cell surface markers CD34+ and CD38−

.

27. The method of claim 21 wherein a plurality of the umbilical cord blood stem cells express the cell surface markers CD34+ and CD38−

.

28. The method of claim 21 wherein a plurality of the umbilical cord blood stem cells express the cell surface markers CD34+ and CD38+.

29. The method of claim 21 wherein the embryonic-like stem cells exhibit or lack at least one of the following cell surface markers:

CD10+, CD29+, CD34−

, CD44+, CD45−

, CD54+, CD90+, SH2+, SH3+, SH4+, SSEA3-, SSEA4-, OCT-4+ and ABC-p+.

30. The method of claim 29 wherein the embryonic-like stem cells are OCT-4+ and ABC-p+.

31. The method of claim 29 wherein the embryonic-like stem cells are SSEA3−

and SSEA4−

.

32. The method of claim 21 wherein the plurality of umbilical cord blood stem cells and the plurality of embryonic-like stem cells are mixed prior to or at the time of administration to a patient in need thereof.

33. The method of claim 21 wherein the plurality of umbilical cord blood stem cells and the plurality of embryonic-like stem cells are physically mixed.

34. The method of claim 21 wherein the plurality of umbilical cord blood stem cells and/or the plurality of embryonic-like stem cells is treated with a growth factor.

35. The method of claim 34 wherein the plurality of umbilical cord blood stem cells and/or the plurality of embryonic-like stem cells is treated with the growth factor to induce differentiation into a particular cell type.

36. The method of claim 34 wherein the plurality of umbilical cord blood stem cells and/or the plurality of embryonic-like stem cells is treated with the growth factor to prevent or suppress differentiation into a particular cell type.

37. The method of claim 21 wherein said patient has a disease, disorder or condition that includes an inflammation component.

38. The method of claim 21 wherein said patient has a vascular disease, disorder or condition.

39. The method of claim 38 wherein said disease, disorder or condition is atherosclerosis.

40. The method of claim 21 wherein said patient has a neurological disease, disorder or condition.

41. The method of claim 40, wherein said disease, disorder or condition is selected from the group consisting of amylotrophic lateral sclerosis and multiple sclerosis.

42. The method of claim 21, wherein said patient has an autoimmune disorder.

43. The method of claim 42 wherein said autoimmune disorder is selected from the group consisting of diabetes and amylotrophic lateral sclerosis.

44. The method of claim 21, wherein said patient has a condition that is caused by or associated with trauma or injury.

45. The method of claim 44, where said trauma or injury is trauma or injury to the central nervous system.

46. The method of claim 44, wherein said trauma or injury is trauma or injury to the peripheral nervous system.

47. A method of treating myelodysplasia which comprises administering umbilical cord blood cells, or stem cells isolated therefrom, and embryonic-like stem cells to a patient in need thereof.

48. The method of claim 47 wherein the administration of the umbilical cord blood cells (or stem cells isolated therefrom) and the administration of the embryonic-like stem cells is concurrent.

49. The method of claim 47 wherein the umbilical cord blood cells (or stem cells isolated therefrom) and the embryonic-like stem cells are combined before administration.

50. A method for transplanting hematopoietic progenitor cells for the treatment or prevention of disease, which method comprises administering umbilical cord blood cells (or stem cells isolated therefrom) and embryonic-like stem cells to a patient in need thereof.

51. The method of claim 50 wherein the administration of the umbilical cord blood cells, or stem cells isolated therefrom, and the administration of the embryonic-like stem cells is concurrent.

52. The method of claim 50 wherein the umbilical cord blood cells, or stem cells isolated therefrom, and the embryonic-like stem cells are combined before administration.

53. A composition which comprises stem or progenitor cells from umbilical cord blood supplemented with a plurality of embryonic-like stem cells.

54. A method of treating a patient in need thereof comprising administration of at least 5×

10⁹ nucleated cells to said patient, said at least 5×

10⁹ nucleated cells comprising embryonic-like stem cells.

55. The method of claim 54 wherein said embryonic-like stem cells are contained in a container.

56. The method of claim 54 wherein said embryonic-like stem cells are suitable for administration to a patient.

57. The method of claim 54 wherein said embryonic-like stem cells are suitable for bone marrow transplantation.

58. The method of claim 54 wherein said embryonic-like stem cells are suitable for administration in humans.

59. The method of claim 54 wherein the embryonic-like stem cells exhibit or lack at least one of the following cell surface markers:

CD10+, CD29+, CD34−

, CD44+, CD45−

, CD54+, CD90+, SH2+, SH3+, SH4+, SSEA3−

, SSEA4−

, OCT-4+ and ABC-p+.

60. The method of claim 59 wherein the embryonic-like stem cells are OCT-4+ and ABC-p+.

61. The method of claim 59 wherein the embryonic-like stem cells are SSEA3−

and SSEA4−

.

62. The method of claim 54 wherein the embryonic-like stem cells are treated with a growth factor.

63. The method of claim 62 wherein the growth factor is a cytokine, lymphokine, interferon, colony stimulating factor (CSF), interferon, chemokine, interleukin, human hematopoietic growth factor, hematopoietic growth factor ligand, stem cell factor, thrombopoeitin (Tpo), granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor, basic fibroblast growth factor, placenta derived growth factor or epidermal growth factor.

64. The method of claim 62 wherein the embryonic-like stem cells are treated with the growth factor to induce differentiation into a plurality of cell types.

65. The method of claim 62 wherein the plurality of embryonic-like stem cells is treated with the growth factor to prevent or suppress differentiation into a particular cell type.

66. The method of claim 54 wherein said treating comprises administering at least 10×

10⁹ total nucleated cells.

67. The method of claim 54 wherein said treating comprises administering at least 20×

10⁹ total nucleated cells.

68. The method of claim 54 wherein said patient has a disease, disorder or condition that includes an inflammation component.

69. The method of claim 54 wherein said patient has a vascular disease, disorder or condition.

70. The method of claim 69 wherein said disease, disorder or condition is atherosclerosis.

71. The method of claim 54 wherein said patient has a neurological disease, disorder or condition.

72. The method of claim 71, wherein said disease, disorder or condition is selected from the group consisting of amylotrophic lateral sclerosis and multiple sclerosis.

73. The method of claim 54, wherein said patient has an immune-related disorder.

74. The method of claim 73 wherein said autoimmune disorder is selected from the group consisting of allergies, diabetes and amylotrophic lateral sclerosis.

75. The method of claim 54, wherein said patient has a condition that is caused by or associated with trauma or injury.

76. The method of claim 75, where said trauma or injury is trauma or injury to the central nervous system.

77. The method of claim 75, wherein said trauma or injury is trauma or injury to the peripheral nervous system.

78. The method of claim 54, wherein said at least 5×

10⁹ nucleated cells comprises a pool of cells derived from a plurality of donors.

79. The method of claim 54 wherein none of said cells in said at least 5×

10⁹ nucleated cells is HLA-typed prior to said administration.

80. The method of claim 54 wherein said at least 5×

10⁹ nucleated cells is preconditioned for between 18 hours and 21 days prior to said administration.

81. The method of claim 54 wherein said at least 5×

10⁹ nucleated cells is preconditioned for between 48 hours and 10 days prior to said administration.

82. The method of claim 54, wherein said at least 5×

10⁹ nucleated cells is preconditioned for between 3-5 days prior to said administration.