Oligodendrocyte Production From Multipotent Neural Stem Cells

Abstract

This invention relates to methods of producing oligodendrocytes from multipotent neural stem cells by using at least one oligodendrocyte promoting factor, particularly granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 3 or interleukin 5. The neural stem cells may optionally be expanded prior to being subjected to the oligodendrocyte promoting factor.

1 - 40 . (canceled) 
   
   
       41 . A method of producing oligodendrocytes from mammalian multipotent neural stem cells, comprising contacting multipotent neural stem cells in a mammal with an effective amount of granulocyte-macrophage colony stimulating factor (GM-CSF). 
   
   
       42 . The method of  claim 41 , further comprising contacting the multipotent neural stem cells with triiodothyronine. 
   
   
       43 . The method of  claim 41 , wherein the multipotent neural stem cells are located in the subventricular zone of the mammal. 
   
   
       44 . The method of  claim 41 , wherein the multipotent neural stem cells are selected from the group consisting of human, dog, cat, rodent, sheep, goat, cattle, horse, pig, and non-human primate cells. 
   
   
       45 . The method of  claim 41 , wherein the multipotent neural stem cells are human cells. 
   
   
       46 . The method of  claim 41 , further comprising contacting the multipotent neural stem cells with an effective amount of at least one biological agent that is capable of increasing the number of multipotent neural stem cells. 
   
   
       47 . The method of  claim 46 , wherein the biological agent is selected from the group consisting of epidermal growth factor (EGF), fibroblast growth factor (FGF), pituitary adenylate cyclase-activating polypeptide (PACAP), transforming growth factor α (TGF α), ciliary neurohophic factor (CNTF), estrogen, ovarian hormone, prolactin, growth hormone, and insulin-like growth factor 1. 
   
   
       48 . The method of  claim 46 , wherein the biological agent is EGF51N. 
   
   
       49 . The method of  claim 46 , wherein the multipotent neural stem cells are contacted with the granulocyte-macrophage colony stimulating factor (GM-CSF) and the biological agent concurrently. 
   
   
       50 . The method of  claim 46 , wherein the multipotent neural stem cells are contacted with the biological agent prior to being contacted with the granulocyte-macrophage colony stimulating factor (GM-CSF). 
   
   
       51 . The method of  claim 41 , wherein the granulocyte-macrophage colony stimulating factor (GM-CSF) is administered systemically to the mammal. 
   
   
       52 . The method of  claim 41 , further comprising transplanting neural stem cells into the mammal. 
   
   
       53 . The method of  claim 52 , wherein the neural stem cells are transplanted into the brain of the mammal. 
   
   
       54 . The method of  claim 52 , wherein the neural stem cells are transplanted into the spinal cord of the mammal. 
   
   
       55 . The method of  claim 52 , wherein the neural stem cells are transplanted into the mammal prior to administering the granulocyte-macrophage colony stimulating factor (GM-CSF) to the mammal. 
   
   
       56 . A method for treating or ameliorating a demyelinating disease in a mammal, comprising administering to the mammal an effective amount of granulocyte-macrophage colony stimulating factor (GM-CSF). 
   
   
       57 . The method of  claim 56 , wherein the granulocyte-macrophage colony stimulating factor (GM-CSF) is administered into a ventricle in the brain of the mammal. 
   
   
       58 . The method of  claim 56 , wherein the granulocyte-macrophage colony stimulating factor (GM-CSF) is administered into the lateral ventricle of the mammal. 
   
   
       59 . The method of  claim 56 , further comprising administering to the mammal an effective amount of at least one biological agent capable of increasing the number of neural stem cells. 
   
   
       60 . The method of  claim 59 , wherein the biological agent is selected from the group consisting of epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), fibroblast growth factor (FGF), transforming growth factor α (TGF α), ciliary neurotrophic factor (CNTF), estrogen, ovarian hormone, prolactin, growth hormone, and insulin-like growth factor 1. 
   
   
       61 . The method of  claim 59 , wherein the biological agent is EGF51N. 
   
   
       62 . The method of  claim 59 , wherein the granulocyte-macrophage colony stimulating factor (GM-CSF) and the biological agent are administered concurrently to the mammal. 
   
   
       63 . The method of  claim 59 , wherein the biological agent is administered to the mammal prior to administering the granulocyte-macrophage colony stimulating factor (GM-CSF) to the mammal. 
   
   
       64 . The method of  claim 56 , wherein the granulocyte-macrophage colony stimulating factor (GM-CSF) is administered systemically to the mammal. 
   
   
       65 . The method of  claim 56 , further comprising administering triiodothyronine to the mammal. 
   
   
       66 . The method of  claim 56 , wherein the demyelinating disease is selected from the group consisting of multiple sclerosis, acute disseminated encephalomyelitis, diffuse cerebral sclerosis, necrotizing hemonhagic encephalitis and leukodystrophies. 
   
   
       67 . The method of  claim 56 , wherein the demyelinating disease is multiple sclerosis. 
   
   
       68 . The method of  claim 56 , wherein the mammal is human. 
   
   
       69 . The method of  claim 56 , further comprising transplanting neural stem cells into the mammal. 
   
   
       70 . The method of  claim 69 , wherein the neural stem cells are transplanted into the brain of the mammal. 
   
   
       71 . The method of  claim 69 , wherein the neural stem cells are transplanted into the spinal cord of the mammal. 
   
   
       72 . The method of  claim 69 , wherein the neural stem cells are transplanted into the mammal prior to administering the granulocyte-macrophage colony stimulating factor (GM-CSF) to the mammal.