Methods for regulation of stem cells

Abstract

Methods are provided for increasing stem cells, hematopoietic progenitor/stem cells, mesenchymal progenitor/stem cells, mesodermal progenitor/stem cells, muscle progenitor/stem cells, or neural progenitor/stem cells in vivo in a mammalian subject. Methods are also provided for treating an immune related disease, a mesenchymal/mesoderm degenerative disease, or a neurodegenerative disease in a mammalian subject in need thereof.

1 . A method for increasing hematopoietic stem cells in vivo in a mammalian subject comprising:
 interacting one or more Wnt/β-catenin signal-, Notch signal-, or Hedgehog signal-promoting agents with the hematopoietic stem cells in the mammalian subject and   increasing the hematopoietic stem cells in the mammalian subject compared to the hematopoietic stem cells in the mammalian subject before treatment.   
     
     
         2 . The method of  claim 1 , wherein the Wnt/β-catenin signal-, Notch signal-, or Hedgehog signal-promoting agent is a polypeptide, nucleic acid, small molecule, antisense oligonucleotide, ribozyme, RNAi construct, siRNA, shRNA, or antibody. 
     
     
         3 . The method of  claim 1 , wherein increasing hematopoietic stem cells in the subject is a result of cell proliferation, cell homing, decreased apoptosis, self-renewal, or increased cell survival. 
     
     
         4 . A method of treating an immune related disease in a mammalian subject in need thereof comprising:
 administering one or more Wnt/β-catenin signal-, Notch signal-, or Hedgehog signal-promoting agents to the subject; and   interacting the one or more Wnt/β-catenin signal-, Notch signal-, or Hedgehog signal-promoting agents with hematopoietic stem cells, and thereby increasing in vivo hematopoietic stem cells in the subject to treat the immune related disease compared to the hematopoietic stem cells in the mammalian subject before treatment.   
     
     
         5 . The method of  claim 4 , wherein the immune related disease is diabetes, graft vs. host disease, immunodeficiency disease, hematopoietic malignancy, hematopoietic failure or hematopoietic stem cell transplantation. 
     
     
         6 . The method of  claim 4 , wherein increasing hematopoietic stem cells in the subject is a result of cell proliferation, cell homing, decreased apoptosis, self-renewal, or increased cell survival. 
     
     
         7 . A method of treating a degenerative disease in a mammalian subject in need thereof comprising:
 administering one or more Wnt/β-catenin signal-, Notch signal-, Hedgehog signal-promoting agents to the subject; and   increasing in vivo one or more mesenchymal progenitor/stem cells in the subject to treat the degenerative disease compared to the progenitor/stem cells in the mammalian subject before treatment.   
     
     
         8 . The method of  claim 7 , further comprising increasing in vivo one or more mesenchymal progenitor/stem cells or mesodermal progenitor/stem cells in the subject to treat a degenerative muscle disease. 
     
     
         9 . The method of  claim 7 , further comprising increasing in vivo one or more mesenchymal progenitor/stem cells or mesodermal progenitor/stem cells in the subject to treat a degenerative liver disease. 
     
     
         10 . The method of  claim 7 , further comprising increasing in vivo one or more mesenchymal progenitor/stem cells or mesodermal progenitor/stem cells in the subject to treat a degenerative pancreatic disease. 
     
     
         11 . The method of  claim 7 , further comprising increasing in vivo one or more mesenchymal progenitor/stem cells or mesodermal progenitor/stem cells in the subject to treat a degenerative endothelial disease. 
     
     
         12 . The method of  claim 7 , wherein the Wnt/β-catenin signal-, Notch signal-, or Hedgehog signal-promoting agent is a polypeptide, nucleic acid, small molecule, antisense oligonucleotide, ribozyme, RNAi construct, siRNA, shRNA, or antibody.