Cell populations which co-express CD49c and CD90

• US 9,969,977 B2
• Filed: 09/20/2002
• Issued: 05/15/2018
• Est. Priority Date: 09/20/2002
• Status: Active Grant

• Current Assignee: Garnet Biotherapeutics Incorporated
• Original Assignee: Garnet Biotherapeutics Incorporated
• Inventors: Ho, Tony W., Kopen, Gene C., Righter, William F., Rutkowski, J. Lynn, Wagner, Joseph, Herring, W. Joseph, Ragaglia, Vanessa
• Primary Examiner(s): Claytor, Renee
• Application Number:
  US10/251,685
• Publication Number:
  US 20040058412A1
• Time in Patent Office: 5,716 Days
• Field of Search: None
• 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: C12N 2501/06 Anti-neoplasic drugs, anti-retroviral drugs, e.g. azacytidine, cyclophosphamide
• CPC Class Codes: C12N 2501/405 Cell cycle regulated proteins, e.g. cyclins, cyclin-dependant kinases
• CPC Class Codes: C12N 2506/11 from blood or immune system cells
• CPC Class Codes: C12N 5/0634 Cells from the blood or the immune system
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells

Abstract

Substantially homogenous cells populations which co-express CD49c, CD90 and telomerase are made. In one embodiment, humans suffering from a degenerative, traumatic, acute injury, cardiac or neurological condition are treated with the substantially homogenous cells populations which co-express CD49c, CD90 and telomerase. In another embodiment, committed progenitor cells are made are made by selecting from a cultured source of a cell population which co-express CD49c and CD90 and modifying the cell population. The committed progenitor cells can be employed to treat a human suffering from a degenerative, traumatic, acute injury, cardiac or neurological condition and to formulate pharmaceutical compositions. In a further embodiment, a substantially homogenous population of cells which co-express CD49c, CD90 and at least one cardiac-related transcription factor is made and can be used to treat a human suffering from a cardiac condition.

Claims

1. An isolated cell population induced to express at least one cardiac-related transcription factor, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c and CD90, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

2. The isolated cell population of claim 1, wherein the cells of the cell population that co-express CD49c and CD90 further co-express telomerase.

3. The isolated cell population of claim 1, wherein the bone marrow is human bone marrow.

4. The isolated cell population of claim 1, wherein the cardiac-related transcription factor is selected from the group consisting of GATA4, Irx4 and Nkx2.5.

5. The isolated cell population of claim 1, further including a label.

6. The isolated cell population of claim 1, wherein the cells of the cell population that co-express CD49c and CD90 differentiate into cardiac muscle cells.

7. The isolated cell population of claim 1, wherein the cells of the cell population that co-express CD49c and CD90 further express at least one trophic factor selected from the group consisting of:

i) brain-derived neurotrophic factor (BDNF)

ii) nerve growth factor (NGF)

iii) neurotrophin-3 (NT-3)

iv) interleukin-6 (IL-6)

v) interleukin-7 (IL-7)

vi) interleukin-11 (IL-11)

vii) stem cell factor (SCF)

viii) macrophage chemoattractant protein-1 (MCP-1)

ix) matrix metalloproteinase-9 (MMP-9)

x) cystatin-C; and

,

xi) vascular endothelial growth factor (VEGF).

8. An isolated cell population induced to express at least one cardiac-related transcription factor, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c and CD90, but does not express bone sialoprotein, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

9. The isolated cell population of claim 8, wherein the cardiac-related transcription factor is selected from the group consisting of GATA4, Irx4 and Nkx2.5.

10. An isolated cell population induced to express GATA4, Irx4 and Nkx2.5, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c and CD90, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

11. An isolated cell population induced to express GATA4, Irx4 and Nkx2.5, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c, CD90, and telomerase, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

12. A pharmaceutical composition comprising an isolated cell population induced to express at least one cardiac-related transcription factor, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c and CD90, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

13. A pharmaceutical composition comprising an isolated cell population induced to express at least one cardiac-related transcription factor, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c, CD90, and telomerase, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

14. A pharmaceutical composition comprising an isolated cell population induced to express GATA4, Irx4 and Nkx2.5, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c, CD90, and telomerase, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

15. A pharmaceutical composition comprising an isolated cell population induced to express GATA4, Irx4 and Nkx2.5, wherein the cell population is derived from bone marrow, wherein greater than about 91% of the cells of the cell population co-express CD49c and CD90, and wherein the cell population is capable of maintaining a doubling rate of less than about 30 hours after 30 cell doublings.

16. An isolated cell population obtainable from human bone marrow and induced to express at least one cardiac-related transcription factor by steps that comprise:

a) incubating human bone marrow cells under a low oxygen condition such that said cells when allowed to adhere to a tissue culture-treated surface will produce adherent colony forming units (CFU);

b) passaging cells in said adherent CFU at a seeding density of less than about 2500 cells/cm²; and

,

c) treating the passaged cells with a protein kinase C inhibitor and a DNA methylation inhibitor

wherein greater than about 91% of said passaged cells co-express CD49c and CD90, and wherein said passaged cells maintain a population doubling rate of less than about 30 hours after 30 cell doublings.