Methods of expanding stem and progenitor cells and expanded cell populations obtained thereby
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-005/00
C12N-005/08
C12N-005/02
출원번호
US-0418639
(2003-04-18)
등록번호
US-7344881
(2008-03-18)
발명자
/ 주소
Peled,Tony
Treves,Avi
Rosen,Oren
출원인 / 주소
Gamida Cell Ltd.
대리인 / 주소
Elrifi,Ivor R.
인용정보
피인용 횟수 :
8인용 특허 :
136
초록▼
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 main
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.
대표청구항▼
What is claimed is: 1. A method of ex vivo expanding a population of hematopoietic stem and/or progenitor cells, while at the same time reversibly inhibiting differentiation of the stem and/or progenitor cells, the method comprising: providing the stem and/or progenitor cells with conditions for ce
What is claimed is: 1. A method of ex vivo expanding a population of hematopoietic stem and/or progenitor cells, while at the same time reversibly inhibiting differentiation of the stem and/or progenitor cells, the method comprising: providing the stem and/or progenitor cells with conditions for cell proliferation and with an effective amount of TEPA-Cu chelate, wherein a free copper concentration available to said cells is not decreased relative to a similar cells not treated with said TEPA-Cu chelate, 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. 2. The method of claim 1, wherein providing said stem and/or progenitor cells with said conditions for cell proliferation include providing said stem and/or progenitor cells with nutrients and cytokines. 3. The method of claim 2, wherein said cytokines are early acting cytokines. 4. The method of claim 3, wherein said early acting cytokines are selected from the group consisting of stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and interleukin-3. 5. The method of claim 2, wherein said cytokines are late acting cytokines. 6. The method of claim 5, wherein said late acting cytokines are selected from the group consisting of granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor and erythropoietin. 7. 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. 8. The method of claim 1, wherein said hematopoietic cells are enriched for CD34+ cells. 9. The method of claim 1, wherein said hematopoietic cells are enriched for stem and/or progenitor cells. 10. The method of claim 1, wherein said cells stem and/or progenitor are selected from the group consisting of non-differentiated stem cells and early progenitor cells. 11. A method of ex vivo expanding a population of hematopoietic stem and/or progenitor cells, while at the same time reversibly inhibiting differentiation of the stem and/or progenitor cells, the method comprising: providing a TEPA-Cu chelate; and thereafter mixing an effective amount of said TEPA-Cu chelate with a cell growth medium, said cell growth medium for providing said stem and/or progenitor cells with conditions for cell proliferation, and with said population of stem and/or progenitor cells, wherein a free copper concentration available to said cells is not decreased relative to a similar cells not treated with said TEPA-Cu chelate by said mixing, 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. 12. The method of claim 11, wherein providing said stem and/or progenitor cells with said conditions for cell proliferation include providing said stem and/or progenitor cells with nutrients and cytokines. 13. The method of claim 12, wherein said cytokines are early acting cytokines. 14. The method of claim 13, wherein said early acting cytokines are selected from the group consisting of stem cell factor, FLT3 ligand, interleukin-6, thrombopoietin and interleukin-3. 15. The method of claim 12, wherein said cytokines are late acting cytokines. 16. The method of claim 15, wherein said late acting cytokines are selected from the group consisting of granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor and erythropoietin. 17. The method of claim 11, wherein said hematopoietic cells are derived from a source selected from the group consisting of bone marrow, peripheral blood and neonatal umbilical cord blood. 18. The method of claim 11, wherein said hematopoietic cells are enriched for stem and/or progenitor cells. 19. The method of claim 11, wherein said hematopoietic cells are enriched for CD34+ cells. 20. The method of claim 11, wherein said stem and/or progenitor cells are selected from the group consisting of non-differentiated stem cells and progenitor cells. 21. A method of ex vivo expanding a population of hematopoietic stem and/or progenitor cells, while at the same time reversibly inhibiting differentiation of the stem and/or progenitor cells, the method comprising: (a) obtaining from a donor a mixed population of cells said mixed population of cells comprises the stem and/or progenitor cells; and (b) culturing said mixed population of cells ex vivo under conditions for proliferation of said stem and/or progenitor cells and with an effective amount of a TEPA-Cu chelate, 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. 22. The method of claim 21, wherein said stem and/or progenitor cells are selected from the group consisting of non-differentiated stem cells and early progenitor cells. 23. The method of claim 21, wherein said mixed population of cells is derived from a source selected from the group consisting of bone marrow, peripheral blood and neonatal umbilical cord blood. 24. The method of claim 21, wherein said mixed population of cells includes a mononuclear fraction of neonatal umbilical cord blood cells. 25. The method of claim 21, wherein said conditions for proliferation of said stem and/or progenitor cells include providing said mixed population of cells with nutrients and cytokines. 26. The method of claim 25, wherein said cytokines are early acting cytokines. 27. The method of claim 26, wherein said early acting cytokines are selected from the group consisting of stem cell factor, FLT3 ligand, interleukin-6, thrombopoietin and interleukin-3. 28. The method of claim 25, wherein said cytokines are late acting cytokines. 29. The method of claim 28, wherein said late acting cytokines are selected from the group consisting of granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor and erythropoietin. 30. The method of claim 21 further comprising separating said stem or/or progenitor cells from said mixed population of cells.
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