In Vivo and Ex Vivo Expansion of Hematopoietic Stem Cells With a Targeted Combination of Clinically Tested, FDA Approved Drugs

Abstract

The present invention provides a therapeutic approach to maintain and expand HSCs in vivo using currently available medications that target GSK-3 and mTOR. The present invention also provides a system and method for the ex vivo culturing of HSCs, where an mTOR inhibitor is combined with a GSK-3 inhibitor within the culturing conditions.

What is claimed: 
     
         1 . A culturing medium for expanding and maintaining a hematopoietic stem cell (HSC), comprising at least one glycogen synthase kinase-3 (GSK-3) inhibitor and at least one mammalian target of rapamycin (mTOR) inhibitor. 
     
     
         2 . The culturing medium of  claim 1 , wherein the culturing medium is capable of maintaining the multipotentiality of an HSC when the HSC is maintained or expanded in the culturing medium. 
     
     
         3 . The culturing medium of  claim 1 , further comprising at least one cytokine. 
     
     
         4 . The culturing medium of  claim 1 , further comprising a promotion factor. 
     
     
         5 . The culturing medium of  claim 1 , wherein the GSK-3 inhibitor is lithium, or a salt thereof. 
     
     
         6 . The culturing medium of  claim 1 , wherein the mTOR inhibitor is rapamycin. 
     
     
         7 . The culturing medium of  claim 1 , further comprising a culture medium component selected from the group consisting of: inorganic salts, carbohydrates, hormones, essential amino acids, vitamins, RPMI 1640, HEPES, FCS, antibiotics, and combinations thereof. 
     
     
         8 . The culturing medium of  claim 1 , wherein the medium is configured to achieve an HCS expansion of about 1-fold expansion to about 200-fold expansion.