Use of marrow-derived glial progenitor cells as gene delivery vehicles into the central nervous system

Abstract

The present disclosure relates to a method for introducing a hematopoietic cell into the brain of a mammal, by administering bone marrow-derived progenitor cells into the body of the mammal by intravenous injection. The bone marrow-derived cell is preferably a cell that differentiates into a glial cell. The disclosure also relates to a method for delivery of therapeutic protein molecules into the brain of a mammal, by administering to a mammal an effective amount of bone marrow-derived progenitor cells which contain a gene having a nucleic acid sequence that encodes a functional therapeutic protein. Isolated recombinant cells and a pharmaceutical composition are also provided.

1 . A method of treating ischemia in the brain of a subject, comprising: 
 administering harvested bone marrow cells to a subject; and    allowing the bone marrow cells to migrate to an ischemic region in the brain of the subject, thereby treating the ischemic region in the brain of the subject.    
   
   
       2 . The method of  claim 1 , wherein the bone marrow cells are transfected with a glial cell line-derived neurotrophic factor (GDNF) gene.  
   
   
       3 . The method of  claim 1 , wherein the bone marrow cells differentiate into astroglia and microglia in the brain of the subject.  
   
   
       4 . The method of  claim 1 , wherein the bone marrow cells migrate to the cortex, hippocampus, thalamus, brainstem or cerebellum of the brain.  
   
   
       5 . The method of  claim 2 , wherein the harvested bone marrow cells are transfected with a vector comprising the GDNF gene.  
   
   
       6 . The method of  claim 5 , wherein the vector is a retroviral vector.  
   
   
       7 . The method of  claim 6 , wherein the retroviral vector is a Moloney murine leukemia virus vector.  
   
   
       8 . The method of  claim 1 , further comprising culturing the harvested bone marrow in vitro in a cell culture medium comprising IL-3, IL-6, and stem cell factor prior to the administering step.  
   
   
       9 . The method of  claim 1 , wherein the subject has been sub-lethally irradiated prior to administration of the harvested bone marrow cells.  
   
   
       10 . A method of treating cortical ischemia, comprising: 
 culturing harvested bone marrow cells in a cell culture medium comprising IL-3, IL-6, and stem cell factor;    transfecting the harvested bone marrow cells with a Moloney murine leukemia virus vector comprising a gene for glial cell line-derived neurotrophic factor (GDNF);    administering the transfected cells intravenously to a subject having cortical ischemia; and    allowing the transfected cells to migrate to the brain of the subject and express the GDNF gene, thereby treating the cortical ischemia.    
   
   
       11 . A method of increasing glial cells in the brain of a subject, comprising: 
 administering harvested bone marrow cells to a subject; and    allowing the bone marrow cells to migrate to the brain of a subject and differentiate into glial cells, thereby increasing glial cells in the brain of the subject.    
   
   
       12 . The method of  claim 11 , wherein the glial cells are astroglia and/or microglia.  
   
   
       13 . The method of  claim 11 , wherein the bone marrow cells migrate to the cortex, hippocampus, thalamus, brainstem, cerebellum, or an ischemic region of the brain.  
   
   
       14 . The method of  claim 11 , further comprising culturing the harvested bone marrow in vitro in a cell culture medium comprising IL-3, IL-6, and stem cell factor prior to the administering step.  
   
   
       15 . The method of  claim 11 , wherein the subject has been sub-lethally irradiated prior to administration of the harvested bone marrow cells.