Methods of expanding myeloid cell populations and uses thereof

Abstract

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.

What is claimed is: 
     
         1 . A method of preparing a therapeutic composition for transiently reconstituting hematopoiesis in a mammalian host, comprising:
 a) culturing a starting cell population including hematopoietic stem cells ex vivo in a culture medium comprising a cytokine and growth factor mixture to expand the myeloid progenitor cells within said cell population; and   b) resuspending said myeloid progenitor cells in a pharmaceutically acceptable medium suitable for administration to a mammalian host.   
     
     
         2 . The method according to  claim 1 , further comprising cryopreserving said expanded myeloid progenitor cells prior to said resuspending step. 
     
     
         3 . The method according to  claim 1 , wherein said starting cell population has been previously cryopreserved. 
     
     
         4 . The method according to  claim 1 , wherein said starting cell population is enriched hematopoietic stem cells. 
     
     
         5 . The method according to  claim 1 , wherein said starting cell population is purified hematopoietic stem cells. 
     
     
         6 . The method according to  claim 5 , wherein said purified hematopoietic stem cells are isolated CD34+CD90+ cells. 
     
     
         7 . The method according to  claim 1 , wherein said hematopoietic stem cells are from plurality allogeneic donors. 
     
     
         8 . The method according to  claim 7 , wherein the allogeneic donors are at least partially mismatched at the MHC with respect to each other. 
     
     
         9 . A method for preparing a therapeutic composition comprising a substantially pure population of non-myeloid cells, said method comprising: expanding myeloid progenitor cells by the method according to  claim 1 , removing from the expanded cell population said myeloid progenitor cells, and resuspending the remaining non-myeloid cells in a pharmaceutically acceptable medium suitable for administration to a mammalian host. 
     
     
         10 . A therapeutic composition comprising expanded myeloid progenitor cells obtained by the method according to  claim 1 . 
     
     
         11 . A therapeutic composition comprising ex vivo expanded myeloid progenitor cells, wherein said myeloid progenitor cells are a mixture of allogeneic myeloid progenitor cells. 
     
     
         12 . The therapeutic composition of  claim 11 , wherein said expanded myeloid progenitor cells are cryopreserved in a cryopreseration medium. 
     
     
         13 . The therapeutic composition of  claim 11 , wherein said expanded myeloid progenitor cells are suspended in a pharmaceutically acceptable carrier. 
     
     
         14 . The therapeutic composition of  claim 11  in which the allogeneic myeloid progenitor cells are at least partially mismatched at the MHC. 
     
     
         15 . The therapeutic composition of  claim 11  in which the allogeneic myeloid progenitor cells are fully mismatched at the MHC. 
     
     
         16 . The therapeutic composition of  claim 11  in which the allogeneic myeloid progenitor cells are isolated common myeloid progenitor cells. 
     
     
         17 . The therapeutic composition of  claim 11  in which the allogeneic myeloid progenitor cells are isolated granulocyte/macrophage progenitor cells. 
     
     
         18 . The therapeutic composition of  claim 11  in which the allogeneic myeloid progenitor cells are isolated megakaryocyte/erythroid progenitor cells. 
     
     
         19 . A method of treating a human patient suffering from impaired hematopoiesis, comprising administering to said patient a therapeutic composition according to  claim 11 . 
     
     
         20 . The method according to  claim 19 , further comprising co-administering isolated HSC cells.