TREATMENT OF MULTIPLE SCLEROSIS USING PLACENTAL STEM CELLS

• US 20100183571A1
• Filed: 01/14/2010
• Published: 07/22/2010
• Est. Priority Date: 10/13/2005
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: EDINGER, James, PALUDAN, Casper, HARBACHEUSKI, Ryhor, MURRAY, RoseAnn, HARIRI, Robert J.
• Granted Patent: US 8,216,566 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61P 17/00 Drugs for dermatological 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 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 25/28 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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: C12N 2502/11 blood or immune system cells
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources

Abstract

The present invention provides methods of immunomodulation using placental stem cells and placental stem cell populations. The invention also provides methods of producing and selecting placental cells and cell populations on the basis of immunomodulation, and compositions comprising such cells and cell populations.

Claims

1-46. -46. (canceled)

47. A method of treating an individual having multiple sclerosis comprising administering a therapeutically effective amount of placental stem cells to the individual in an amount sufficient to detectably improve one or more symptoms of multiple sclerosis in the individual, wherein said placental stem cells detectably suppress T cell proliferation stimulated by Epstein-Barr virus antigen-presenting B cells;

and

wherein at least 80% of said placental stem cells express CD200.

48. The method of claim 47, wherein said therapeutically effective amount is an amount sufficient to detectably improve one or more symptoms of multiple sclerosis in the individual

49. The method of claim 47, comprising administering 1 million to 10 billion placental stem cells to said individual.

50. The method of claim 49, comprising administering 1×

10⁶ placental stem cells to said individual.

51. The method of claim 49, comprising administering 1×

10⁷ placental stem cells.

52. The method of claim 49, comprising administering 1×

10⁸ placental stem cells.

53. The method of claim 49, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are OCT-4⁺.

54. The method of claim 49, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are one or more of CD34⁻

, CD38⁻

, or CD45⁻

.

55. The method of claim 53, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are one or more of CD34⁻

, CD38⁻

, or CD45⁻

.

56. The method of claim 49, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are CD10⁺ or CD105⁺.

57. The method of claim 53, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are CD10⁺ or CD105⁺.

58. The method of claim 49, wherein said at least 80% of said 1 million to 10 billion said placental stem cells are CD10⁺, CD34⁻

, CD105⁺ and CD200⁺.

59. The method of claim 47, wherein said one or more symptoms comprises or more of a sensory disturbance in the limbs, an optic nerve dysfunction, a pyramidal tract dysfunction, a bladder dysfunction, a bowel dysfunction, a sexual dysfunction, ataxia, or diplopia.

60. The method of claim 47, wherein said individual demonstrates and improvement on the Expanded Disability Status Scale of at least one point.

61. The method of claim 47, wherein said individual demonstrates and improvement on the Expanded Disability Status Scale of at least two points.

62. The method of claim 47, wherein said individual has relapsing/remitting multiple sclerosis or progressive/relapsing multiple sclerosis.

63. The method of claim 47, wherein said individual has secondary progressive multiple sclerosis or primary progressive multiple sclerosis.

64. The method of claim 47, wherein said placental stem cells are administered during an acute attack of multiple sclerosis in said individual.

65. The method of claim 47, comprising administering a second type of stem cell to said individual.

66. The method of claim 65, wherein said second type of stem cell is mesenchymal stem cells from bone marrow.

67. The method of claim 47, additionally comprising administering to said individual a therapeutic agent, wherein said therapeutic agent is adrenocorticotropic hormone (ACTH), methylprednisolone, dexamethasone, IFNβ

-1a, IFN-1b, gliatriamer acetate, cyclophosphamide, methotrexate, azathioprine, cladribine, cyclosporine, mitoxantrone, or sulfasalazine.

68. The method of claim 47, wherein said placental stem cells have been cryopreserved prior to said administration.

69. The method of claim 47, wherein said placental stem cells have been passaged no more than 10 times prior to said administration.

70. A method of treating an individual having multiple sclerosis, comprising administering to the individual a therapeutically effective amount of placental multipotent cells, or culture medium conditioned by placental multipotent cells, wherein said multipotent placental cells are CD34⁻

, CD10⁺ and CD105⁺, as detected by flow cytometry, and adherent to tissue culture plastic, and wherein the therapeutically effective amount is an amount sufficient to cause a detectable improvement in one or more symptoms of said multiple sclerosis.

71. The method of claim 70, wherein said CD34⁻

, CD10⁺, CD105⁺ multipotent placental cells are additionally CD200⁺, as detected by flow cytometry.

72. The method of claim 71, wherein said CD34⁻

, CD10⁺, CD105⁺, CD200⁺ multipotent placental cells are additionally one or more of CD45⁻

, CD133⁻

, CD13⁺, CD44⁺, CD90⁺, or HLA-G⁺, as detected by flow cytometry.

73. The method of claim 71, wherein said CD34⁻

, CD10⁺, CD105⁺, CD200⁺ multipotent placental cells are additionally CD45⁻

, CD133⁻

, CD13⁺, CD44⁺, CD90⁺, and HLA-G⁺, as detected by flow cytometry.

74. The method of claim 70, wherein said multiple sclerosis is relapsing/remitting multiple sclerosis.

75. The method of claim 70, wherein said multiple sclerosis is secondary progressive multiple sclerosis.

76. The method of claim 70, wherein said multiple sclerosis is primary progressive multiple sclerosis.

77. The method of claim 70, wherein said multiple sclerosis is progressive/relapsing multiple sclerosis.

78. The method of claim 70, wherein said symptom of multiple sclerosis is a sensory disturbance in a limb, an optic nerve dysfunction, a pyramidal tract dysfunction, a bladder dysfunction, a bowel dysfunction, a sexual dysfunction, ataxia, or diplopia.

79. The method of claim 70, wherein administering results in an improvement on the Expanded Disability Status Scale (EDSS) of at least one half point.