USE OF THE OPPOSITE CELL DIFFERENTIATION PROGRAM (OCDP) FOR THE TREATMENT OF DEGENERATED ORGANS IN THE PATHOLOGICAL STATE

• US 20100278786A1
• Filed: 04/18/2008
• Published: 11/04/2010
• Est. Priority Date: 09/18/2007
• Status: Active Grant

• Current Assignee: Eberhard Karls Universitaet Tuebingen Medizinische Fakultaet
• Original Assignee: Universitã¤T Leipzig
• Inventors: Danielyan, Lusine, Proksch, Barbara, Gleiter, Christoph, Buniatian, Gayane, Gebhardt, Rolf
• Granted Patent: US 9,157,065 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• 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: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 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 2502/14 hepatocytes
• CPC Class Codes: C12N 5/0622 Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells

Abstract

The present invention relates to a method for the treatment of organs which are degenerative and/or in the pathological state by means of the use of cells, which are phenotypically stably differentiating or differentiated but not necessarily ultimately predetermined with respect to development, from a donor organ selected according to the principles of the opposite cell differentiation program (OCDP) and also to the use of cells of this type for the treatment or for the production of a drug for treatment of the same. Furthermore, the present invention relates to pharmaceutical agents comprising suitable phenotypically stable cells, cells of a first organ which is different from the second organ with respect to organ type thereby being used, which, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, have opposite properties to the second cells in the normal physiological state.

Claims

1. A use of phenotypically stably differentiating or differentiated cells as donor cells (first cells) for the production of a drug for the treatment of a second organ of an organism, which organ is degenerated and/or in the pathological stage, with second cells which are degenerated and/or in the pathological stage, there being used as donor cells, cells of a first organ which is different from the second organ with respect to organ type, which, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, have opposite properties to the second cells in the normal physiological state.

2. A use of phenotypically stably differentiating or differentiated cells as donor cells (first cells) for the treatment of a second organ of an organism, which organ is degenerated and/or in the pathological stage, with second cells which are degenerated and/or in the pathological stage, there being used as donor cells, cells of a first organ which is different from the second organ with respect to organ type, which, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, have opposite properties to the second cells in the normal physiological state.

3. A method for the treatment of an organ (second organ) of an organism, which organ is degenerated and/or in the pathological stage, with cells (second cells) which are degenerated and/or in the pathological stage, in which the phenotypically stably differentiating or differentiated cells are applied as donor cells (first cells) of a first organ which is different from the second organ with respect to organ type, which, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, have opposite properties to the second cells in the normal physiological state.

4. The method according to claim 3, wherein the second cells in the degenerated and/or pathological state, compared with their normal physiological state, have opposite properties with respect to the predetermined set of expressed genes and/or phenotypical properties.

5. The method according to claim 3, wherein the donor cells in their normal, physiological state with respect to the predetermined set of expressed genes and/or phenotypical properties are equivalent to the cells which are degenerated and/or in the pathological state and/or have the same properties.

6. The method according to claim 3, wherein the donor cells, compared with the second cells with respect to the predetermined set of expressed genes and/or phenotypical properties, have an opposite differentiation program from the normal, physiological state in a degenerated and/or pathological state.

10. The method according to claim 3, wherein the phenotypically stably differentiating or differentiated cells are in a normal physiological state.

15. The method according to claim 3, wherein both the second cells and the donor cells or both the cells of the first cell type and of the second cell type in their respective organ have functions for organ tissue homeostasis, material transfer between different organ compartments, organ detoxification and/or organ regeneration.

16. The method according to claim 15, wherein the expressed genes and/or phenotypical properties of the predetermined set fulfill functions within the scope of organ tissue homeostasis, material transfer between different organ compartments, organ detoxification and/or organ regeneration.

17. The method according to claim 3, at least one or more predetermined functions and/or properties of the cells of the organ, which is degenerated and/or in the pathological stage, or of the cells of the second type being reduced and/or missing.

18. The method according to claim 3, the organism being a vertebrate and/or mammal.

19. The method according to claim 3, the organism being a human.

20. The method according to claim 3, the donor cells or cells of the first cell type producing protective factors as predetermined cell properties and/or functions.

21. The method according to claim 3, the donor cells or cells of the first cell type producing one or more factors which are specific for the second cells or cells of the second type and promote growth and/or regeneration, said factors being not produced or produced insufficiently by the second cell or cells of the second cell type.

22. The method according to claim 3, GFAP-positive cells, in particular perivascular GFAP-positive cells, being used/applied.

23. The method according to claim 22, the used/applied cells producing erythropoietin and/or BDNF and/or metallothionein and/or glutamine synthetase and/or NGF and/or collagen type 1 and/or GPR 49 and/or further protective factors.

24. The method according to claim 3, glia cells being used/applied.

25. The method according to claim 3 for the treatment of fibrosing diseases of a non-neural organ, phenotypically stably differentiating or differentiated astrocytes or cells which have a similar differentiation program being used/applied.

26. The method according to claim 3 for the treatment of cirrhosis of the liver, phenotypically stably differentiating or differentiated astrocytes or cells which have a similar differentiation program being used/applied.

27. The method according to claim 25 for the treatment of kidney fibrosis, phenotypically stably differentiating or differentiated astrocytes or cells which have a similar differentiation program being used/applied.

28. The method according to claim 3 for the treatment of neurodegenerative diseases, phenotypically stably differentiating or differentiated hepatic stellate cells and/or mesangial cells or cells which have a similar differentiation program being used/applied.

29. The method according to claim 3 for the treatment of diseases which are characterized by a loss of neurons and/or their functionality and/or a disorder of the organ-specific homeostasis, phenotypically stably differentiating or differentiated hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts being used/applied.

30. The method according to claim 3 for the treatment of Alzheimer'"'"'s disease, phenotypically stably differentiating or differentiated hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts being used/applied.

31. The method according to claim 3 for the treatment of multiple sclerosis, phenotypically stably differentiating or differentiated hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts being used/applied.

32. The method according to claim 3 for the treatment of Parkinson'"'"'s disease, phenotypically stably differentiating or differentiated hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts being used/applied.

33. The method according to claim 3 for the treatment of stroke, phenotypically stably differentiating or differentiated hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts being used/applied.

7. A use of phenotypically stably differentiating or differentiated cells of a specific first cell type of an organism for the production of a drug for the protection and/or regeneration of cells, which are degenerated and/or in the pathological stage, of a specific second cell type of an organism, the cells of the first cell type, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, having opposite properties to the cells of the second cell type in the normal physiological state.

8. A use of phenotypically stably differentiating or differentiated cells of a specific first cell type of an organism for the protection and/or regeneration of cells, which are degenerated and/or in the pathological stage, of a specific second cell type of an organism, the cells of the first cell type, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, having opposite properties to the cells of the second cell type in the normal physiological state.

9. A method for the protection and/or regeneration of cells, which are degenerated and/or in the pathological stage, of a specific second type of an organism, in which phenotypically stably differentiating or differentiated cells of a specific first cell type of an organism are applied, the cells of the first cell type, in the normal physiological state with respect to a specific set of expressed genes and/or phenotypical properties, having opposite properties to the cells of the second cell type in the normal physiological state.

11. The method according to claim 9, wherein the cells of the second cell type, in the degenerated and/or pathological state, have opposite properties with respect to a predetermined set of expressed genes and/or phenotypical properties relative to their normal physiological state.

12. The method according to claim 9, wherein the cells of the first cell type, in the normal physiological state with respect to a predetermined set of expressed genes and/or phenotypical properties, are equivalent to the cells of the second cell type which are degenerated and/or in the pathological state and/or have the same properties.

13. The method according to claim 9, wherein the cells of the first cell type, in the normal physiological state, have counter and/or opposite activation, regulation and/or differentiation states with respect to a predetermined set of expressed genes and/or phenotypical properties relative to the cells of the second cell type which are degenerated and/or in the pathological state.

14. The method according to claim 9, wherein, with respect to a predetermined set of expressed genes and/or phenotypical properties, the degree of activation, regulation and/or differentiation of the cells of the first cell type in the normal physiological state is opposite to the degree of activation, regulation and/or differentiation of the cells of the second cell type which are degenerated and/or in the pathological state.

34. A pharmaceutical agent, comprising, with respect to at least one or more predetermined cell properties and/or functions, phenotypically stably differentiating or differentiated cells.

35. The pharmaceutical agent according to claim 34, wherein the phenotypically stably differentiating or differentiated cells produce protective factors as predetermined cell properties and/or functions.

36. The pharmaceutical agent according to claim 34, wherein the phenotypically stably differentiating or differentiated cells are GFAP-positive cells, in particular perivascular GFAP-positive cells.

37. The pharmaceutical agent according to claim 34, wherein the phenotypically stably differentiating or differentiated cells are glia cells.

38. The pharmaceutical agent according to claim 34, wherein the phenotypically stably differentiating or differentiated cells are astrocytes or cells which have a similar differentiation program.

39. The pharmaceutical agent according to claim 34, wherein the phenotypically stably differentiating or differentiated cells are hepatic stellate cells, mesangial cells, stellate cells of the pancreas, dendritic cells of the spleen and/or skin fibroblasts.