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 . (canceled) 
     
     
         2 . A method for increasing hematopoietic stem or progenitor cells in a mammalian subject comprising:
 (a) selecting a mammalian subject in need of an increase in hematopoietic stem or progenitor cells;   (b) treating a population of hematopoietic stem or progenitor cells in vitro with a Wnt/β-catenin signal-promoting agent; and   (c) administering the treated population of hematopoietic stem or progenitor cells to the selected mammalian subject;   wherein the amount of hematopoietic stem or progenitor cells is increased in the selected mammalian subject receiving the treated hematopoietic stem or progenitor cells compared to a mammalian subject receiving untreated hematopoietic stem or progenitor cells.   
     
     
         3 . The method of  claim 2 , wherein the population of hematopoietic stem or progenitor cells comprises umbilical cord blood cells, fetal liver cells, bone marrow cells, or peripheral blood cells. 
     
     
         4 . The method of  claim 2 , wherein the hematopoietic stem or progenitor cells are autologous or allogeneic hematopoietic stem or progenitor cells. 
     
     
         5 . The method of  claim 2 , wherein the hematopoietic stem or progenitor cells are adult hematopoietic stem or progenitor cells. 
     
     
         6 . The method of  claim 2 , wherein the hematopoietic progenitor cells are selected from the group consisting of: erythroid cells; granulocyte cells; macrophage cells; granulocyte-macrophage cells; B cells; T cells; and multipotent mixed lineage colony type cells. 
     
     
         7 . The method of  claim 2 , wherein increasing the hematopoietic stem or progenitor cells in the selected mammalian subject is a result of increased engraftment, cell proliferation, cell homing, decreased apoptosis, self renewal, or increased cell survival. 
     
     
         8 . The method of  claim 2 , wherein the Wnt/β-catenin signal-promoting agent is a polypeptide, a nucleic acid, a small molecule, an antisense oligonucleotide, a ribozyme, an RNAi construct, an siRNA, an shRNA, or an antibody. 
     
     
         9 . The method of  claim 2 , wherein the Wnt/β-catenin signal-promoting agent comprises a Wnt1 agonist, Wnt3a agonist, or Wnt8 agonist, or a glycogen synthase kinase (GSK) inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the GSK inhibitor is a small molecule. 
     
     
         11 . The method of  claim 2 , wherein administration of the hematopoietic stem or progenitor cells to the subject is carried out by intravesicular, intrathecal, parenteral, topical, intravenous, oral, inhalant, subcutaneous, intraarterial, intracranial, intraperitoneal, intranasal, or intramuscular administration. 
     
     
         12 . The method of  claim 2 , wherein the mammalian subject has an immune related disease. 
     
     
         13 . The method of  claim 12 , wherein the immune related disease is selected from the group consisting of graft vs. host disease, immunodeficiency disease, hematopoietic malignancy, hematopoietic failure, and hematopoietic stem cell transplantation. 
     
     
         14 . The method of  claim 13 , wherein the hematopoietic malignancy is selected from the group consisting of chronic myeloid leukemia, acute myeloid leukemia, non-Hodgkins's lymphoma, multiple myeloma, chronic lymphocytic leukemia, Hodgkin's disease, and myelodysplastic syndrome. 
     
     
         15 . The method of  claim 13 , wherein the immunodeficiency disease is selected from the group consisting of primary immunodeficiency, hemoglobinopathy, and single gene disorders. 
     
     
         16 . The method of  claim 2 , wherein the source of the treated hematopoietic stem cells or progenitor cells is selected from the group consisting of umbilical cord blood cells, bone marrow cells, and peripheral blood cells.