[미국특허]
Methods of controlling proliferation and differentiation of stem and progenitor cells
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-005/00
C12N-005/08
출원번호
US-0084528
(2005-03-18)
등록번호
US-7312078
(2007-12-25)
발명자
/ 주소
Peled,Tony
Fibach,Eitan
Treves,Avi
출원인 / 주소
Gamida Cell Ltd.
Hadasit Medical Research Services and Development, Ltd.
대리인 / 주소
Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
인용정보
피인용 횟수 :
3인용 특허 :
135
초록▼
A method of ex-vivo expanding a population of stem cells, while at the same time inhibiting differentiation of the stem cells. The method comprises ex-vivo providing the stem cells with conditions for cell proliferation and with at least one copper chelator in an amount and for a time period for per
A method of ex-vivo expanding a population of stem cells, while at the same time inhibiting differentiation of the stem cells. The method comprises ex-vivo providing the stem cells with conditions for cell proliferation and with at least one copper chelator in an amount and for a time period for permitting the stem cells to proliferate and, at the same time, for reducing a capacity of the stem cells to differentiate.
대표청구항▼
What is claimed is: 1. An ex-vivo expanded hematopoietic cell population comprising cells having reduced available intracellular copper and characterized by a greater clonogenic potential, engraftment potential, immune system reconstitution potential and/or proportion of CD34+ positive cells, as co
What is claimed is: 1. An ex-vivo expanded hematopoietic cell population comprising cells having reduced available intracellular copper and characterized by a greater clonogenic potential, engraftment potential, immune system reconstitution potential and/or proportion of CD34+ positive cells, as compared to ex vivo hematopoietic cells cultured in a presence of cytokines and having normal levels of available intracellular copper. 2. The expanded hematopoietic cell population of claim 1, wherein said cells are provided in a culture medium. 3. The expanded hematopoietic cell population of claim 2, wherein said culture medium comprises cytokines and a transition metal chelator having affinity for copper. 4. The expanded hematopoietic cell population of claim 1, wherein said cells are isolated from a culture medium. 5. A pharmaceutical composition comprising the expanded hematopoietic cell population of claim 1. 6. A pharmaceutical composition comprising the expanded hematopoietic cell population of claim 3. 7. The expanded hematopoietic cell population of claim 1, wherein said cells originate from hematopoietic stem or progenitor cells. 8. The expanded hematopoietic cell population of claim 1, wherein said hematopoietic cells are from a source selected from the group consisting of peripheral blood, bone marrow and neonatal umbilical cord blood. 9. The expanded hematopoietic cell population of claim 1, wherein said cells originate from CD34+ enriched cells. 10. The expanded hematopoietic cell population of claim 1, wherein said cells originate from neonatal umbilical cord blood cells. 11. The expanded hematopoietic cell population of claim 1, wherein said expanded hematopoietic cell population is expanded in a culture medium comprising cytokines and a transition metal chelator having affinity for copper. 12. The expanded hematopoietic cell population of claim 11, wherein said transition metal chelator is selected from the group consisting of polyamine chelating agents, ethylendiamine, diethylenetriamine, triethylenetetramine, triethylenediamine, tetraethylenepentamine, aminoethylethanolamine, aminoethylpiperazine, pentaethylenehexamine, triethylenetetramine-hydrochloride, tetraethylenepentamine-hydrochloride, pentaethylenehexamine-hydrochloride, tetraethylpentamine, captopril, penicilamine, N,N'-bis(3-aminopropyl)-1,3-propanediamine, N,N,Bis (2 animoethyl) 1,3 propane diamine, 1,7-dioxa-4,10-diazacyclododecane, 1,4,8,11-tetraaza cyclotetradecane-5,7-dione, 1,4,7-triazacyclononane trihydrochloride, 1-oxa-4,7,10-triazacyclododecane, 1,4,8,12-tetraaza cyclopentadecane or 1,4,7,10-tetraaza cyclododecane, preferably tetraethylpentamine. 13. The expanded hematopoietic cell population of claim 11, wherein said transition metal chelator is tetraethylenepentamine. 14. The expanded hematopoietic cell population of claim 13, wherein said transition metal chelator concentration is about 0.1 μM to about 100 mM. 15. The expanded hematopoietic cell population of claim 14, wherein said transition metal chelator concentration is about 4 μM to about 50 mM. 16. The expanded hematopoietic cell of claim 15, wherein said transition metal chelator concentration is about 5 μM to about 40 mM. 17. The expanded hematopoietic cell population of claim 11, wherein said cytokines are early acting cytokines. 18. The expanded hematopoietic cell population of claim 17, wherein said early acting cytokines are selected from the group consisting of stem cell factor, FLT3 ligand, interleukin-6, thrombopoietin and interleukin-3. 19. The expanded hematopoietic cell population of claim 18, wherein said early acting cytokine is FLT3 ligand. 20. The expanded hematopoietic cell population of claim 11, wherein said cytokines are late acting cytokines. 21. The expanded hematopoietic cell population of claim 20, wherein said late acting cytokines are selected from the group consisting of granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor and erythropoietin. 22. The expanded hematopoietic cell population of claim 21, wherein said late acting cytokine is granulocyte colony stimulating factor.
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