CD34 Stem Cell-Related Methods and Compositions

Abstract

This invention provides novel stem cell-based methods for treating a number of conditions. These methods employ CD34 − stem cells, and have a tremendous advantage in that they do not require myeloablation in the subject being treated. The CD34 − stem cells used in the instant methods can be genetically modified or not, depending on the disorder treated.

1 . A method for treating a subject afflicted with a gastrointestinal disorder comprising introducing into the subject's bloodstream a therapeutically effective number of CD34 −  stem cells, wherein (a) the CD34 −  stem cells are not genetically modified, (b) the introduction of the CD34 −  stem cells is not preceded, accompanied or followed by myeloablation, and (c) the gastrointestinal disorder is characterized by a need for cell proliferation in the gastrointestinal endothelium. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . A method for treating a diabetic subject or a pre-diabetic subject comprising introducing into the subject's bloodstream a therapeutically effective number of CD34 −  stem cells, wherein (a) the CD34 −  stem cells are not genetically modified, and (b) the introduction of the CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         8 - 17 . (canceled) 
     
     
         18 . A method for treating a subject afflicted with muscular dystrophy comprising introducing into the subject's bloodstream a therapeutically effective number of non-autologous CD34 −  stem cells, wherein (a) the CD34 −  stem cells are not genetically modified, and (b) the introduction of the CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         19 - 22 . (canceled) 
     
     
         23 . A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone surgery comprising introducing into the subject's bloodstream a therapeutically effective number of CD34 −  stem cells, wherein (a) the CD34 −  stem cells are introduced into the subject's bloodstream immediately prior to, during, and/or immediately following surgery, (b) the CD34 −  stem cells are not genetically modified, and (c) the introduction of the CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         24 - 30 . (canceled) 
     
     
         31 . A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone a physical trauma comprising introducing into the subject's bloodstream a therapeutically effective number of CD34 −  stem cells, wherein (a) the CD34 −  stem cells are introduced into the subject's bloodstream immediately prior to, during, and/or immediately following the physical trauma, (b) the CD34 −  stem cells are not genetically modified, and (c) the introduction of the CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         32 - 38 . (canceled) 
     
     
         39 . A method for treating a subject afflicted with a tumor comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter/enhancer combination, whereby the cytotoxic protein is selectively expressed when the genetically modified CD34 −  stem cells come into proximity with, and differentiate in proximity with, tumor tissue undergoing angiogenesis, and (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         40 - 45 . (canceled) 
     
     
         46 . A method for treating a subject afflicted with a gastrointestinal disorder comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation, and (c) the gastrointestinal disorder is characterized by a need for cell proliferation in the gastrointestinal endothelium. 
     
     
         47 - 52 . (canceled) 
     
     
         53 . A method for treating a diabetic subject or a pre-diabetic subject comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         54 - 64 . (canceled) 
     
     
         65 . A method for treating a subject afflicted with muscular dystrophy comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which is absent from or under-expressed in the subject's muscle cells or whose overexpression in the subject's muscle cells is desired, which region is operably linked to (ii) a muscle-specific promoter or muscle-specific promoter/enhancer combination, and (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         66 - 73 . (canceled) 
     
     
         74 . A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone surgery comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         75 - 82 . (canceled) 
     
     
         83 . A method for improving microcirculation and/or acute wound healing in a subject who is about to undergo, is undergoing or has undergone a physical trauma comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified CD34 −  stem cells, wherein (a) each of the genetically modified CD34 −  stem cells contains an exogenous nucleic acid comprising (i) a region encoding a protein which enhances endothelial cell growth, which region is operably linked to (ii) an endothelium-specific promoter or promoter/enhancer combination, and (b) the introduction of the genetically modified CD34 −  stem cells is not preceded, accompanied or followed by myeloablation. 
     
     
         84 - 91 . (canceled)