MAINTENANCE/EXPANSION OF HSC's

• US 20110311492A1
• Filed: 12/01/2009
• Published: 12/22/2011
• Est. Priority Date: 12/01/2008
• Status: Abandoned Application

• Current Assignee: Katholieke Universiteit Leuven KU Leuven R&D, Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Katholieke Universiteit Leuven KU Leuven R&D, Regents of The University of Minnesota (University of Minnesota)
• Inventors: Verfaillie, Catherine, Buckley, Shannon Mychel, Khurana, Satish
• Application Number:
  US13/132,283
• Publication Number:
  US 20110311492A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C12N 2502/02 embryonic cells
• CPC Class Codes: C12N 2502/14 hepatocytes
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The invention is related to methods for culturing stem cells, more particularly hematopoietic stem cells (HSC). The invention relates to methods for HSC maintenance and/or expansion through the use of soluble factors. The invention is also directed to cells produced by the methods of the invention. The cells are useful, among other things, for treatment of disorders or diseases (e.g. leukemia). The invention also relates to the development of small molecules that may increase HSC self renewal in vitro and in vivo.

Claims

1. A method to maintain/expand hematopoietic stem cells (HSCs) comprising contacting HSCs with at least one or more exogenous factors selected from TFPI, DEFCR3, SERPINE2, COL18A1, BGLAP, COL8A1, INHBA, LTBP2, MAC30, a biologically active fragment or derivative thereof so as to maintain/expand said HSCs.

3. The method of claim 1, wherein the one or more factors are SERPINE2 and/or Tfpi.

5. The method of claim 1, wherein the HSCs are further contacted with one or more growth factors or cytokines.

7. The method of claim 1, wherein the maintained/expanded HSCs are long-term-repopulating (LTR-) HSCs.

8. The method of claim 7, wherein the LTR-HSCs are competitive repopulation (CR)-long-term-repopulating (LTR-) HSC.

9. The method of claim 1, wherein the maintained/expanded HSCs are short-term-repopulating (STR-) HSCs.

12. Cells produced according to the method of claim 1.

13. A composition comprising the cells of claim 12.

2. (canceled)

4. (canceled)

6. (canceled)

10-11. -11. (canceled)

14. A composition comprising HSCs and one or more factors selected from TFPI, DEFCR3, SERPINE2, COL18A1, BGLAP, COL8A1, INHBA, LTBP2, MAC30, a biologically active fragment or derivative thereof.

16. The composition of claim 14, where the one or more factors are SERPINE2 and/or Tfpi.

17. The composition of claim 14 further comprising a cytokine or growth factor.

15. (canceled)

18. (canceled)

19. A method to prepare a composition comprising combining one or more factors selected from TFPI, DEFCR3, SERPINE2, COL18A1, BGLAP, COL8A1, INHBA, LTBP2, MAC30, a biologically active fragment or derivative thereof with HSCs.

21. The method of claim 19, wherein the one or more factors are SERPINE2 and/or Tfpi.

22. The method of claim 19 further comprising adding a cytokine or growth factor.

20. (canceled)

23. (canceled)

24. A method to treat a non-malignant blood disorder, a metabolic storage disorder or cancer comprising administering to a subject in need thereof HSCs which have been contacted with one or more factors selected from TFPI, DEFCR3, SERPINE2, COL18A1, BGLAP, COL8A1, INHBA, LTBP2, MAC30, a biologically active fragment or derivative thereof so as to treat a non-malignant blood disorder, a metabolic storage disorder or cancer in the subject.

26. The method of claim 24, where the one or more factors are SERPINE2 and/or Tfpi.

27. The method of claim 24, wherein the HSCs have further been contacted with a cytokine.

25. (canceled)

28-35. -35. (canceled)

36. A method to treat a non-malignant blood disorder, a metabolic storage disorder or cancer comprising administering to a subject in need thereof one or more factors selected from TFPI, DEFCR3, SERPINE2, COL18A1, BGLAP, COL8A1, INHBA, LTBP2, MAC30, a biologically active fragment or derivative thereof so as to treat a non-malignant blood disorder, a metabolic storage disorder or cancer in the subject.

38. The method of claim 36, where the one or more factors is SERPINE2 and/or Tfpi.

39. The method of claim 36, further comprising administering a cytokine.

37. (canceled)

40-44. -44. (canceled)