Adipose tissue derived stromal cells for the treatment of neurological disorders

• US 20070104697A1
• Filed: 11/23/2005
• Published: 05/10/2007
• Est. Priority Date: 02/26/2000
• Status: Active Grant

• Current Assignee: Vetstem Biopharma, Inc.
• Original Assignee: Artecel Inc.
• Inventors: Vanguri, Padmavathy, Gimble, Jeffrey, Wilkison, William
• Granted Patent: US 7,582,292 B2
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• 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: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

The present invention relates to a treatment of neural injury and neurodegenerative diseases. Also included in the present invention is the use of adipose tissue derived stromal cells for the treatment of neural injury (stroke, traumatic brain injury, spinal cord injury) and neurodegeneration (i.e. Parkinson'"'"'s disease).

Claims

1. A method of treating a mammal suffering from a disease, disorder or condition of the central nervous system, the method comprising administering an adipose tissue derived stromal cell to the central nervous system of said mammal, wherein the presence of said stromal cell in the central nervous system effects treatment of said disease, disorder or condition.

2. The method of claim 1, wherein said stromal cell is selected from the group consisting of an autologous stromal cell, an allogeneic stromal cell, a syngeneic stromal cell and a xenogeneic stromal cell, with respect to said mammal.

3. The method of claim 1, wherein said stromal cell is derived from a human donor.

4. The method of claim 1, wherein said mammal is a human.

5. 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, an ischemic induced injury, a spinal cord injury, stroke and Parkinson'"'"'s disease.

6. The method of claim 5, wherein said disease, disorder or condition is injury to a tissue or a cell of said central nervous system.

7. The method of claim 5, wherein said disease, disorder or condition is within the brain of said mammal.

8. The method of claim 1, wherein said stromal cell administered to said central nervous system remains present or replicates in said central nervous system.

9. The method of claim 1, wherein prior to administering said stromal cell, said stromal cell is cultured in vitro for a period of time to differentiate into a cell that expresses at least one protein characteristic of a neuronal cell.

10. The method of claim 1, wherein said stromal cell is administered to said mammal by a route selected from the group consisting of intravascular, intracerebral, parenteral, intraperitoneal, intravenous, epidural, intraspinal, intrasternal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, and intramuscular.

11. The method of claim 1, wherein said stromal cell in the central nervous system of the mammal secretes a factor selected from the group consisting of a growth factor, a trophic factor and a cytokine.

12. The method of claim 11, wherein said factor is selected from the group consisting of leukemia inhibitory factor (LIF), brain-derived neurotrophic factor (BDNF), epidermal growth factor receptor (EGF), basic fibroblast growth factor (bFGF), FGF-6, glial-derived neurotrophic factor (GDNF), granulocyte colony-stimulating factor (GCSF), hepatocyte growth factor (HGF), IFN-γ

, insulin-like growth factor binding protein (IGFBP-2), IGFBP-6, IL-1ra, IL-6, IL-8, monocyte chemotactic protein (MCP-1), mononuclear phagocyte colony-stimulating factor (M-CSF), neurotrophic factors (NT3), tissue inhibitor of metalloproteinases (TIMP-1), TIMP-2, tumor necrosis factor (TNF-β

), vascular endothelial growth factor (VEGF), VEGF-D, urokinase plasminogen activator receptor (uPAR), bone morphogenetic protein 4 (BMP4), IL1-a, IL-3, leptin, stem cell factor (SCF), stromal cell-derived factor-1 (SDF-1), platelet derived growth factor-BB (PDGFBB), transforming growth factors beta (TGFβ

-1) and TGFβ

-3.

13. The method of claim 1, wherein prior to administering said stromal cell to said mammal, said stromal cell is transfected with an isolated nucleic acid encoding a therapeutic protein, wherein when said protein is secreted by said stromal cell, said protein serves to enhance treatment of said disease, disorder or condition.

14. The method of claim 1, wherein said stromal cell is administered to said mammal at the site of injury.

15. The method of claim 1, wherein said stromal cell is administered to said mammal at an adjacent site to the site of injury.

16. The method of claim 15, wherein following administering said stromal cell to said mammal, said stromal cell migrates to the site of injury.

17. The method of claim 1, wherein said stromal cell in the central nervous system activates the proliferation of neighboring cells.

18. The method of claim 17, wherein said neighboring cells are astrocytes.

19. The method of claim 17, wherein said neighboring cells are neural progenitor cells.

20. The method of claim 17, wherein said neighboring cells are neural progenitor cells and astrocytes.

21. The method of claim 1, wherein said stromal cell in the central nervous system activates the differentiation of neighboring cells.

22. The method of claim 1, wherein said stromal cell in the central nervous system expresses at least one protein characteristic of a cell of the central nervous system.

23. The method of claim 22, wherein said stromal cell expresses at least one protein characteristic of a cell of the central nervous system selected from the group consisting of class III β

-tubulin, the M subunit of neurofilaments, tyrosine hydroxylase, glutamate receptor subunits of the GluR1-4 and GluR6 classes, glial fibrillary acidic protein, myelin basic protein, brain factor 1, NeuN, NF-M, NSE, nestin, and trkA.

24. The method of claim 1, wherein said stromal cell is administered concomitantly with at least one factor selected from the group consisting of a trophic factor, a growth factor, a cytokine, a neurotrophin, or any combination thereof.

25. The method of claim 1, where said stromal cell is administered to the mammal in the absence of an immunosuppressive agent.