Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells

Abstract

The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.

1 - 55 . (canceled) 
     
     
         56 . A kit comprising, in one or more containers:
 (a) a Notch agonist, and   (b) 4-(2-(2-(benzothiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol (SR1).   
     
     
         57 . The kit of  claim 56 , wherein the Notch agonist and the SR1 are in separate containers. 
     
     
         58 . The kit of  claim 56 , wherein the Notch agonist is an extracellular domain of a Delta protein or a Jagged protein, or a Notch-binding portion of any of the foregoing. 
     
     
         59 . The kit of  claim 58 , wherein the domain or portion is fused to a fusion partner. 
     
     
         60 . The kit of  claim 59 , wherein the fusion partner is an Fc region of an IgG. 
     
     
         61 . The kit of  claim 58 , wherein the Notch agonist is an extracellular domain of a Delta protein. 
     
     
         62 . The kit of  claim 58 , wherein the Notch agonist is Delta ext-IgG . 
     
     
         63 . The kit of  claim 62 , wherein the Delta ext-IgG  is present in the container at a concentration between about 0.2 and 20 μg/ml. 
     
     
         64 . The kit of  claim 62 , wherein the Delta ext-IgG  is present in the container at a concentration between about 1.25 and 10 μg/ml. 
     
     
         65 . (canceled) 
     
     
         66 . The kit of  claim 56 , wherein the kit comprises a solid phase on which the Notch agonist is immobilized. 
     
     
         67 . (canceled) 
     
     
         68 . The kit of  claim 62 , wherein the kit comprises a solid phase on which Delta ext-IgG  is immobilized. 
     
     
         69 . The kit of  claim 68 , wherein the Delta ext-IgG  has been applied to the solid phase at a concentration between about 0.2 and 20 μg/ml. 
     
     
         70 . The kit of  claim 68 , wherein the Delta ext-IgG  has been applied to the solid phase at a concentration between about 1.25 and 10 μg/ml. 
     
     
         71 . (canceled) 
     
     
         72 . The kit of  claim 56 , further comprising a fibronectin or a fragment thereof. 
     
     
         73 . The kit of  claim 72 , wherein the kit comprises a fragment of fibronectin, wherein the fragment of fibronectin is CH-296, immobilized on the solid phase. 
     
     
         74 . (canceled) 
     
     
         75 . (canceled) 
     
     
         76 . The kit of  claim 56 , further comprising one or more growth factors. 
     
     
         77 . The kit of  claim 76 , wherein the growth factors are selected from stem cell factor (SCF), Flt-3 ligand (Flt-3), Interleukin-6 (IL-6), Interleukin-3 (IL-3), Interleukin-11 (IL-11), thrombopoietin (TPO), Granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF). 
     
     
         78 . The kit of  claim 76 , comprising three or more growth factors. 
     
     
         79 . The kit of  claim 78 , comprising IL-6, Flt-3, SCF and TPO. 
     
     
         80 . The kit of  claim 78 , comprising IL-6, Flt-3, SCF, TPO and IL-3. 
     
     
         81 - 103 . (canceled)