Methods of expanding stem and progenitor cells and expanded cell populations obtained thereby

• US 7,655,225 B2
• Filed: 02/19/2008
• Issued: 02/02/2010
• Est. Priority Date: 01/25/2002
• Status: Expired due to Fees

• Current Assignee: Gamida Cell, Ltd.
• Original Assignee: Gamida Cell, Ltd.
• Inventors: Treves, Avi, Peled, Tony, Rosen, Oren
• Primary Examiner(s): Belyavskyi; Michail A
• Application Number:
  US12/070,543
• Publication Number:
  US 20080279828A1
• Time in Patent Office: 714 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: C12N 2500/20 Transition metals
• 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 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

Ex vivo and in vivo methods of expanding a population of stem and/or progenitor cells, while at the same time reversibly inhibiting differentiation of the stem and/or progenitor cells by providing the stem and/or progenitor cells with an effective amount of at least one copper chelate, so as to maintain a free copper concentration available to said cells substantially unchanged, to thereby expand the population of said stem and/or progenitor cells, while at the same time reversibly inhibit differentiation of said stem and/or progenitor cells.

Claims

1. A method of hematopoietic stem and/or progenitor cells transplantation comprising:

(a) obtaining the hematopoietic stem and/or progenitor cells to be transplanted from a donor;

(b) providing said hematopoietic stem and/or progenitor cells ex-vivo with conditions for cell proliferation and with an effective amount of a TEPA-Cu chelate, wherein total intracellular copper content of said cells increases relative to similar cells not treated with said TEPA-Cu chelate, to thereby expand the population of stem and/or progenitor cells, while at the same time reversibly inhibit differentiation of said stem and/or progenitor cells; and

(c) transplanting said hematopoietic stem and/or progenitor cells to a patient.

5. The method of claim 1, wherein said donor and said patient are a single individual.

6. The method of claim 1, wherein said hematopoietic cells are derived from a source selected from the group consisting of bone marrow, peripheral blood and neonatal umbilical cord blood.

7. The method of claim 1, wherein step (a) further includes enriching said hematopoietic cells for stem and/or progenitor cells.

8. The method of claim 1, wherein step (a) further includes enriching said hematopoietic cells for CD34+ cells.

9. The method of claim 1, wherein step (b) includes providing said hematopoietic cells with nutrients and cytokines.

10. The method of claim 1, wherein said cytokines are early acting cytokines.

11. The method of claim 10, wherein said early acting cytokines are selected from the group consisting of stem cell factor, FLT3 ligand, interleukin-6, thrombopoietin and interleukin-3.

12. The method of claim 9, wherein said cytokines are late acting cytokines.

13. The method of claim 12, wherein said late acting cytokines are selected from the group consisting of granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor and erythropoietin.

2. A method of hematopoietic stem and/or progenitor cells transplantation comprising:

(a) obtaining hematopoietic stem and/or progenitor cells to be transplanted from a donor;

(b) providing a TEPA-Cu chelate; and

thereafter

(c) mixing an effective amount of a TEPA-Cu chelate with a cell growth medium, said cell growth medium for providing said hematopoietic stem and/or progenitor cells with conditions for cell proliferation, and with said hematopoietic stem and/or progenitor cells, wherein total intracellular copper content of said cells increases relative to similar cells not treated with said TEPA-Cu chelate, to thereby expand the population of said hematopoietic stem and/or progenitor cells, while at the same time reversibly inhibit differentiation of said hematopoietic stem and/or progenitor cells; and

(d) transplanting said hematopoietic stem and/or progenitor cells to a patient.

3. A method of adoptive immunotherapy comprising:

(a) obtaining progenitor hematopoietic cells from a patient;

(b) providing said progenitor hematopoietic cells ex-vivo with conditions for cell proliferation and with an effective amount of a TEPA-Cu chelate, wherein total intracellular copper content of said cells increases relative to similar cells not treated with said TEPA-Cu chelate, to thereby expand the population of said progenitor hematopoietic cells, while at the same time reversibly inhibit differentiation of said progenitor hematopoietic cells; and

(c) transplanting said expanded progenitor hematopoietic cells to said patient.

4. A method of adoptive immunotherapy comprising:

(a) obtaining progenitor hematopoietic cells from a patient;

(b) providing a TEPA-Cu chelate; and

thereafter

(c) mixing an effective amount of said TEPA-Cu chelate with a cell growth medium, said cell growth medium for providing said progenitor hematopoietic cells with conditions for cell proliferation, and with said progenitor hematopoietic cells, so as to keep substantially unchanged by said mixing the free copper concentration in said cell growth medium, wherein total intracellular copper content of said cells increases relative to similar cells not treated with said TEPA-Cu chelate, while at the same time reversibly inhibit differentiation of said progenitor hematopoietic cells; and

(d) transplanting said expanded progenitor hematopoietic cells to said patient.