Compositions and methods for promoting hematopoietic stem cell regeneration

Abstract

Described is a method for promoting regeneration of hematopoietic stem and progenitor cells in a subject in need thereof. The method comprises administering to the subject a composition comprising a CaMKK2 inhibitor. The CaMKK2 inhibitor may be a small molecule inhibitor, such as STO-609.

What is claimed is: 
     
         1 . A method of promoting regeneration of hematopoietic stem and progenitor cells (HSPCs) in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a CaMKK2 inhibitor, wherein the CaMKK2 inhibitor is a small molecule inhibitor, an antisense oligonucleotide, an siRNA, an miRNA, an RNAi, or an antibody; and,
 wherein the composition is administered to the subject for less than 5 days following the bone marrow injury in the subject.   
     
     
         2 . The method of  claim 1 , wherein the composition is administered to the subject to promote regeneration of HSPCs following bone marrow injury in the subject. 
     
     
         3 . The method of  claim 2 , wherein the bone marrow injury in the subject is a radiation injury. 
     
     
         4 . The method of  claim 3 , wherein the radiation injury in the subject is caused by total body irradiation. 
     
     
         5 . The method of  claim 1 , wherein the subject has or is at risk of developing acute hematopoietic radiation syndrome. 
     
     
         6 . The method of  claim 1 , wherein the CaMKK2 inhibitor prevents transcription, translation, or activity of CaMKK2. 
     
     
         7 . The method of  claim 1 , wherein the composition is administered to the subject once a day over the course of 1, 2, 3, or 4 days following bone marrow injury. 
     
     
         8 . The method of  claim 7 , wherein the composition is administered to the subject once a day over the course of 3 days following bone marrow injury. 
     
     
         9 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         10 . The method of  claim 9 , wherein the subject is a human. 
     
     
         11 . The method of  claim 1 , wherein the composition is administered systemically to the subject in a dose of 1 mg/kg to 30 mg/kg.