Compositions, kits, and methods for modulating survival and differentiation of multi-potential hematopoietic progenitor cells

• US 6,261,841 B1
• Filed: 06/23/2000
• Issued: 07/17/2001
• Est. Priority Date: 06/25/1999
• Status: Expired due to Fees

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Cohen, Isaac, Lin, Jiandie, Lefebvre, Phil, Linzer, Daniel
• Primary Examiner(s): Weber, Jon P.
• Assistant Examiner(s): Guttman, Harry J
• Application Number:
  US09/602,848
• Time in Patent Office: 389 Days
• Field of Search: 435/383-387, 435/377, 435/2
• US Class Current: 435/387
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/145 Thrombopoietin [TPO]
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/26 Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2501/315 Prolactin
• CPC Class Codes: C12N 5/0644 Platelets; Megakaryocytes
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The invention includes compositions, kits, and methods for modulating survival and differentiation of mammalian multi-potential hematopoietic progenitor cells using a placental glycoprotein hormone of the murine prolactin family, namely either murine prolactin-like protein E or murine prolactin-like protein F. The compositions, kits, and methods described herein can be used, for example, for in vitro or ex vivo expansion of hematopoietic precursor cells or to treat a disorder associated with aberrant hematopoiesis (e.g., pre-eclampsia and thrombocytopenia).

Claims

1. A method of maintaining mammalian hematopoietic progenitor cells in vitro, the method comprising maintaining the cells in vitro in a nutritive medium comprising murine prolactin-like protein E (mPLP-E).

2. The method of claim 1, wherein the mPLP-E has the amino acid sequence SEQ ID NO:

2.

3. The method of claim 2, wherein the mPLP-E is glycosylated at at least one of residues 6, 28, 80, 119, 127, and 234 of SEQ ID NO:

2.

4. The method of claim 1, wherein the nutritive medium further comprises a cytokine selected from the group consisting of thrombopoietin, interleukin-3, interleukin-6, interleukin-11, leukemia inhibitory factor, and kit ligand.

5. The method of claim 1, wherein the nutritive medium further comprises a cytokinc selected from the group consisting of thrombopoietin, interleukin-3, stem cell factor, and flt3 ligand.

6. The method of claim 1, wherein the nutritive medium further comprises thrombopoietin.

7. The method of claim 6, wherein the nutritive medium further comprises stem cell factor and flt3 ligand.

8. The method of claim 1, wherein the nutritive medium further comprises interleukin-3.

9. The method of claim 1, wherein the cells are human hematopoietic progenitor cells.

10. The method of claim 1, wherein the cells are obtained from bone marrow of a mammal.

11. The method of claim 1, wherein the cells are obtained from a fetal mammal.

12. The method of claim 1, wherein the cells are obtained from cord blood.

13. The method of claim 1, wherein the cells are maintained in the nutritive medium for at least about 3 days.

14. A method of inducing proliferation of mammalian hematopoietic progenitor cells in vitro, the method comprising maintaining the cells in vitro in a nutritive medium comprising mPLP-E.

15. A method of expanding mammalian hematopoietic progenitor cells in vitro, the method comprising maintaining the cells in vitro in a nutritive medium comprising mPLP-E.

16. A method of inducing differentiation of mammalian hematopoietic progenitor cells in vitro, the method comprising maintaining the cells in vitro in a nutritive medium comprising mPLP-E.

17. A method of inducing mammalian hematopoietic progenitor cells to differentiate in vitro into megakaryocytes, the method comprising maintaining the cells in vitro in a nutritive medium comprising mPLP-E.

18. A method of inducing mammalian megakaryocytes to differentiate into platelets, the method comprising contacting the megakaryocytes with mPLP-E.

19. The method of claim 18, wherein the megakaryocytes are contacted with mPLP-E in vitro.

20. In an in vitro method of maintaining mammalian hematopoietic progenitor cells, the improvement comprising

maintaining the cells in the presence of mPLP-E.