Bone marrow transplantation for treatment of stroke

• US 20050169896A1
• Filed: 12/30/2004
• Published: 08/04/2005
• Est. Priority Date: 05/14/1999
• Status: Abandoned Application

• Current Assignee: Henry Ford Health System
• Original Assignee: Henry Ford Health System
• Inventors: Li, Yi, Chopp, Michael
• Application Number:
  US11/027,881
• Publication Number:
  US 20050169896A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived 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 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 human patient having a disease, disorder or condition of the central nervous system, the method comprising isolating stromal cells from a bone marrow sample, and administering said stromal cells to the central nervous system of said human patient, wherein the presence of said stromal cells in the central nervous system effects treatment of said disease, disorder or condition, further wherein the presence of said stromal cells in the central nervous system does not induce an immune response against said stromal cells.

2. The method of claim 1, wherein said stromal cells are selected from the group consisting of autologous stromal cells, allogeneic stromal cells, syngeneic stromal cells and xenogeneic stromal cells, with respect to said patient.

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

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

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 within the brain of said patient.

7. The method of claim 1, wherein said 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 stromal cells, said cells are cultured in vitro for a period of time.

9. The method of claim 1, wherein said stromal cells are administered to said patient by a route selected from the group consisting of intravascular, intracerebral, parenteral, intraperitoneal, intravenous, epidural, intraspinal, intrastemal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, and intramuscular.

10. The method of claim 1, wherein said stromal cells in the central nervous system of the patient secrete a factor selected from the group consisting of a growth factor, a trophic factor and a cytokine.

11. The method of claim 10, 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-Ira, 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), IL 1-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.

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

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

17. The method of claim 16, wherein said neighboring cells are astrocytes.

18. The method of claim 16, wherein said stromal cells activate the MEK/Akt pathway in neighboring cells.

19. The method of claim 16, wherein said stromal cells activate the PI3K/Erk pathway in neighboring cells.

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

21. The method of claim 1, wherein said stromal cells in the central nervous system exhibits at least one characteristic of a cell of the central nervous system.

22. The method of claim 21, wherein said stromal cells exhibits at least one characteristic of a cell of the central nervous system selected from the group consisting of class III β

-tubulin, the M subunit of neurofiliments, tyrosine hydroxylase, gluatmate 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.

23. The method of claim 1, wherein said stromal cells are administered concomitantly with growth factors.

24. The method of claim 1, wherein said stromal cells administered into said patient prevent axonal fiber loss in the cells from the patient.

25. The method of claim 1, wherein said stromal cells administered to said patient prevent demyelination in the cells from the patient.

26. The method of claim 1, where said stromal cells are administered into the patient in the absence of immunosupppressive agents.

13. The method of clam 1, wherein said stromal cells are administered to said patient at the site of injury.

14. The method of clam 1, wherein said stromal cells are administered to said patient at an adjacent site to the site of injury.

15. The method of claim 14, wherein following administering said stromal cells into said patient, said stromal cells migrate to the site of injury.