In vivo and ex vivo expansion of hematopoietic stem cells with a targeted combination of clinically tested, FDA approved drugs
View Patent ↗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.
1. A method for the maintenance and expansion of a hematopoietic stem cell (HSC), the method comprising culturing said HSC in a medium comprising at least one glycogen synthase kinase-3 (GSK-3) inhibitor and at least one mammalian target of rapamycin (mTOR) inhibitor, wherein the multipotentiality of the HSC is retained during the culturing.
2. The method of claim 1 , wherein the HSC is derived from a mammal.
3. The method of claim 1 , wherein the mammal is a human.
4. The method of claim 1 , wherein exogenous genetic material has been introduced into the HSC.
5. The method of claim 1 , wherein the medium further comprises at least one cytokine.
6. The method of claim 1 , wherein the medium further comprises a promotion factor.
7. The method of claim 1 , wherein the GSK-3 inhibitor is lithium, or a salt thereof.
8. The method of claim 1 , wherein the mTOR inhibitor is rapamycin.
9. The method of claim 1 , wherein the culturing is ex vivo.