CD34 Stem cell-related methods and compositions

• US 20090041735A1
• Filed: 05/20/2008
• Published: 02/12/2009
• Est. Priority Date: 05/24/2007
• Status: Active Grant

• Current Assignee: Apceth GmbH & Co. KG (Resonac Holdings Corp.)
• Original Assignee: Apceth GmbH & Co. KG (Resonac Holdings Corp.)
• Inventors: Stangl, Manfred J., Raggi, Matthias C., Huss, Ralf, Nelson, Peter C.
• Granted Patent: US 7,998,472 B2
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• 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: 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 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• 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: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 14/49 : Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

This invention provides novel stem cell-based methods for treating a number of conditions. These methods employ CD34⁻ stem cells, and have a tremendous advantage in that they do not require myeloablation in the subject being treated. The CD34⁻ stem cells used in the instant methods can be genetically modified or not, depending on the disorder treated.

Claims

1. A method for treating a subject afflicted with a gastrointestinal disorder comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of CD34⁻

stem cells, wherein (a) the CD34⁻

stem cells are not genetically modified, (b) the introduction of the CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation, and (c) the gastrointestinal disorder is characterized by a need for cell proliferation in the gastrointestinal endothelium.

2-6. -6. (canceled)

7. A method for treating a diabetic subject or a pre-diabetic subject comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of CD34⁻

stem cells, wherein (a) the CD34⁻

stem cells are not genetically modified, and (b) the introduction of the CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

8-17. -17. (canceled)

18. A method for treating a subject afflicted with muscular dystrophy comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of non-autologous CD34⁻

stem cells, wherein (a) the CD34⁻

stem cells are not genetically modified, and (b) the introduction of the CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

19-22. -22. (canceled)

23. A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone surgery comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of CD34⁻

stem cells, wherein (a) the CD34⁻

stem cells are introduced into the subject'"'"'s bloodstream immediately prior to, during, and/or immediately following surgery, (b) the CD34⁻

stem cells are not genetically modified, and (c) the introduction of the CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

24-30. -30. (canceled)

31. A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone a physical trauma comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of CD34⁻

stem cells, wherein (a) the CD34⁻

stem cells are introduced into the subject'"'"'s bloodstream immediately prior to, during, and/or immediately following the physical trauma, (b) the CD34⁻

stem cells are not genetically modified, and (c) the introduction of the CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

32-38. -38. (canceled)

39. A method for treating a subject afflicted with a tumor comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter/enhancer combination, whereby the cytotoxic protein is selectively expressed when the genetically modified CD34⁻

stem cells come into proximity with, and differentiate in proximity with, tumor tissue undergoing angiogenesis, and (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

40-45. -45. (canceled)

46. A method for treating a subject afflicted with a gastrointestinal disorder comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation, and (c) the gastrointestinal disorder is characterized by a need for cell proliferation in the gastrointestinal endothelium.

47-52. -52. (canceled)

53. A method for treating a diabetic subject or a pre-diabetic subject comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

54-64. -64. (canceled)

65. A method for treating a subject afflicted with muscular dystrophy comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which is absent from or under-expressed in the subject'"'"'s muscle cells or whose overexpression in the subject'"'"'s muscle cells is desired, which region is operably linked to (ii) a muscle-specific promoter or muscle-specific promoter/enhancer combination, and (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

66-73. -73. (canceled)

74. A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone surgery comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

75-82. -82. (canceled)

83. A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone a physical trauma comprising introducing into the subject'"'"'s bloodstream a therapeutically effective number of genetically modified CD34⁻

stem cells, wherein (a) each of the genetically modified CD34⁻

stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34⁻

stem cells is not preceded, accompanied or followed by myeloablation.

84-91. -91. (canceled)