Methods of expanding myeloid cell populations and uses thereof
The present disclosure relates to a method of expanding myeloid progenitor cells by culturing an initial population of cells in a medium comprising a mixture of cytokines and growth factors that promote growth and expansion of the myeloid progenitor cells. The expanded cell population provides a source of cells as therapeutic treatments for neutropenia and/or thrombocytopenia arising in patients subjected to myeloablative therapy and hematopoietic stem cell transplantation.
1. A method of improving impaired hematopoiesis in a human, comprising,
administering to the human a composition comprising human expanded allogeneic myeloid progenitor cells derived from multiple unrelated donors and having less than 5% CD34+CD90+ hematopoietic stem cells (HSCs), in an amount sufficient to improve hematopoiesis in the human, wherein there is at least a partial mismatch at a major histocompatability complex (MHC) gene between the donors and the human.
2. The method of claim 1 , wherein the myeloid progenitor cells comprise common myeloid progenitor cells.
3. The method of claim 1 , wherein the myeloid progenitor cells comprise granulocyte/macrophage progenitor cells.
4. The method of claim 1 , wherein the myeloid progenitor cells comprise megakaryocyte/erythroid progenitor cells.
5. The method of claim 1 , wherein the myeloid progenitor cells comprise at least about 85% of cells administered to the human.
6. The method of claim 1 , further comprising administering to the human at least one of an antiviral compound, an anti-fungal compound, an anti-bacterial compound, a cytokine or a growth factor.
7. The method of claim 1 , wherein the human is undergoing hematopoietic stem cell (HSC) transplantation.
8. The method of claim 7 , wherein the expanded myeloid progenitor cells are administered after the HSC transplantation.
9. The method of claim 7 , wherein the expanded myeloid progenitor cells are administered concurrently with HSC transplantation.
10. The method of claim 1 , wherein the human is neutropenic.
11. The method of claim 10 , wherein the expanded myeloid progenitor cells are administered with a therapeutic composition for treating complications associated with neutropenia.
12. The method of claim 11 , wherein the therapeutic composition comprises at least one of an antiviral compound, an anti-fungal compound and an anti-bacterial compound.
13. The method of claim 11 , wherein the therapeutic composition comprises G-CSF or compounds that activate production of granulocytes.
14. The method of claim 11 , wherein the therapeutic composition comprises GM-CSF or compounds that activate production of granulocytes or monocytes.
15. The method of claim 1 , wherein the human is suffering from thrombocytopenia.
16. The method of claim 15 , wherein the expanded myeloid progenitor cells are administered adjunctively with a therapeutic composition for treating complications associated with thrombocytopenia.
17. The method of claim 16 , wherein the therapeutic composition comprises a platelet preparation.
18. The method of claim 16 , wherein the therapeutic composition comprises EPO.
19. The method of claim 1 , wherein there is a complete mismatch in major histocompatability complex (MHC) genes between a donor and the human.
20. The method of claim 1 , wherein the myeloid progenitor cells are expanded from cells obtained from peripheral blood.
21. The method of claim 1 , wherein the myeloid progenitor cells are expanded from cells obtained from bone marrow.
22. The method of claim 1 , wherein the myeloid progenitor cells are expanded from cells obtained from umbilical cord blood or placental cord blood.
23. The method of claim 1 , wherein the human has been previously treated with or exposed to a myeloablative agent.
24. The method of claim 23 , wherein the myeloablative agent is ionizing radiation.
25. The method of claim 24 , wherein exposure to the radiation was unintended.
26. The method of claim 1 , wherein the human has defective hematopoietic stem cell development.
27. The method of claim 1 , further comprising administering thrombopoietin (TPO) to the human.
28. The method of claim 1 , wherein the human is in need of transient reconstitution of hematopoiesis.
29. The method of claim 1 , wherein the human has undergone myeloablation.