ISOLATED STROMAL CELLS FOR USE IN THE TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM

• US 20090214492A1
• Filed: 01/20/2009
• Published: 08/27/2009
• Est. Priority Date: 03/28/1995
• Status: Abandoned Application

• Current Assignee: Philadelphia Health and Education Corp (Drexel University)
• Original Assignee: Philadelphia Health and Education Corp (Drexel University)
• Inventors: Stokes, David G., Azizi, S. Ausim, Prockop, Darwin J.
• Application Number:
  US12/356,427
• Publication Number:
  US 20090214492A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• 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 11/00 Drugs for disorders of the respiratory system
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 14/745 Blood coagulation or fibrinolysis factors
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 16/2845 against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
• CPC Class Codes: C12N 2501/135 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2502/08 : cells of the nervous system
• CPC Class Codes: C12N 2502/1311 : Osteocytes, osteoblasts, odontoblasts
• CPC Class Codes: C12N 2506/1353 : from bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 2799/027 : where the vector is derived from a retrovirus
• CPC Class Codes: C12N 5/0622 : Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12Y 114/16002 : Tyrosine 3-monooxygenase (1.14.16.2)
• CPC Class Codes: C12Y 304/21022 : Coagulation factor IXa (3.4.21.22)

Abstract

Methods of treating a human patient having a disease, disorder or condition of the central nervous system are disclosed. The methods include obtaining a bone marrow sample from a human donor, isolating stromal cells from the bone marrow sample, and administering the isolated stromal cells to the central nervous system of the human patient, wherein the presence of the isolated stromal cells in the brain effects treatment of the disease, disorder or condition. Stromal cells which are isolated may be cultured in vitro, they may be genetically engineered to produce therapeutic compounds, and/or they may be pre-differentiated prior to administration into the central nervous system.

Claims

1. A method of treating a human patient having a disease, disorder or condition of the central nervous system, the method comprising obtaining a bone marrow sample from a human donor, isolating stromal cells from said bone marrow sample, and administering said isolated stromal cells to the central nervous system of said human patient, wherein the presence of said isolated stromal cells in said central nervous system effects treatment of said disease, disorder or condition.

2. The method of claim 1, wherein said human donor is not suffering from a disease, disorder or condition of the central nervous system and wherein said human donor is synergeneic with said patient.

3. The method of claim 1, wherein said human donor is said human patient.

4. The method of claim 1, wherein said disease, disorder or condition of the central nervous system is selected from the group consisting of a genetic disease, a tumor, trauma and stroke.

5. The method of claim 4, wherein said disease, disorder or condition is injury to the tissues or cells of said central nervous system.

6. The method of claim 4, wherein said disease, disorder or condition is a brain tumor.

7. The method of claim 1, wherein said isolated stromal cells administered to said central nervous system remain present or replicate in said central nervous system.

8. The method of claim 1, wherein prior to administering said isolated stromal cells, said cells are cultured in vitro.

9. The method of claim 1, wherein prior to administering said isolated stromal cells, said isolated stromal cells are transfected with an isolated nucleic acid encoding a therapeutic protein, wherein when said protein is expressed in said cells said protein serves to effect treatment of said disease, disorder or condition.

10. The method of claim 9, wherein said therapeutic protein is selected from the group consisting of a cytokine, a chemokine and a neurotrophin.

11. The method of claim 1, wherein prior to administering said isolated stromal cells, said isolated stromal cells are transfected with an isolated nucleic acid encoding a therapeutic protein wherein when such protein is secreted by said cells said protein serves to effect treatment of said disease, disorder or condition.

12. The method of claim 11, wherein said isolated nucleic acid is operably linked to a promoter/regulatory sequence.

13. The method of claim 11, wherein said therapeutic protein is selected from the group consisting of a cytokine, a chemokine and a neurotrophin.

14. The method of claim 9, wherein said isolated nucleic acid is a wild type copy of a mutated, non-functioning or under-expressed gene, wherein said isolated nucleic acid is operably linked to a promoter/regulatory sequence and is expressed in said isolated stromal cells.

15. The method of claim 11, wherein said isolated nucleic acid is a wild type copy of a mutated, non-functioning or under-expressed gene, wherein said isolated nucleic acid is operably linked to a promoter/regulatory sequence and is expressed in to generate a protein which is secreted from said isolated stromal cells.

16. The method of claim 1, wherein prior to administrating said stromal cells, said cells are pre-differentiated by coculturing said stromal cells in the presence of a substantially homogeneous population of differentiated cells, whereby said stromal cells differentiate and acquire the phenotypic characteristics of said differentiated cells.

17. The method of claim 1, wherein prior to administration of said isolated stromal cells at least one of the steps of culturing said cells in vitro, introducing isolated nucleic acid into said cells, and pre-differentiating said cells, is performed.

18. The method of claim 1, wherein said isolated stromal cells are immunologically isolated.

19. A method of directing the differentiation of an isolated stromal cell comprising culturing said isolated stromal cell in the presence of a substantially homogeneous population of differentiated cells whereby said isolated stromal cell differentiates and acquires the phenotypic characteristics of said differentiated cells.

20. The method of claim 19, wherein said differentiated cells are astrocytes.