Compositions and methods for providing hematopoietic function without hla matching

Abstract

The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.

1 . A method of preparing a CD34+ enriched, T cell depleted, expanded human cord blood stem and progenitor cell product, comprising:
 selecting a plurality of umbilical cord blood or placental blood samples without regard to the HLA-type of the samples,   pooling the plurality of samples to form a pooled product;   enriching the number of CD34+ cells in the pooled product;   expanding the enriched CD34+ pooled product in the presence of an immobilized Notch ligand and fibronectin fragments in a culture medium comprising the following human growth factors: 50 ng/ml of stem cell factor, 50 ng/ml of Flt3 ligand, 50 ng/ml of thrombopoietin, 50 ng/ml of IL-6 and 10/ng/ml of IL-3 for at least 10 days; and   cryopreserving the expanded and enriched CD34+ pooled product.   
     
     
         2 . The method of  claim 1 , wherein the enriched CD34+ pooled product has been depleted of T cells and red blood cells. 
     
     
         3 . The method of  claim 1 , wherein the Notch ligand is Delta. 
     
     
         4 . The method of  claim 3 , wherein the Delta is Delta ext-IgG . 
     
     
         5 . The method of  claim 1 , wherein the fibronectin fragments are CH-296 or a recombinant human fibronectin fragment. 
     
     
         6 . The method of  claim 1 , wherein the culture medium further comprises a serum free expansion medium. 
     
     
         7 . The method of  claim 1 , wherein the pooled product comprises at least 3.5 million CD34+ cells. 
     
     
         8 . The method of  claim 1 , wherein the expanded and enriched CD34+ pooled product is cryopreserved in the presence of a cryoprotective agent. 
     
     
         9 . The method of  claim 1 , wherein the expanded and enriched CD34+ pooled product comprises at least 75 million CD34+ cells. 
     
     
         10 . The method of  claim 9 , wherein the expanded and enriched CD34+ pooled product comprises at least 250 million CD34+ cells. 
     
     
         11 . The method of  claim 1 , wherein the pooled product comprises genetically engineered CD34+ cells. 
     
     
         12 . The method of  claim 1 , wherein the expanded and enriched CD34+ pooled product comprises genetically engineered CD34+ cells.