Combined Regulation of Neural Cell Production

Abstract

This invention relates to a method of selectively producing neural cells, including neurons or glial cells, in vitro or in vivo. Also provided are methods of treating or ameliorating neurodegenerative disease or medical conditions by producing neural cells. Thus, a combination of factors is used to achieve two steps: increasing the number of neural stem cells and instructing the neural stem cells to selectively become neurons or glial cells.

1 . A method for producing neuronal precursor cells or glial precursor cells, comprising:
 (a) providing at least one neural stem cell;   (b) contacting the neural stem cell with a factor selected from the group consisting of prolactin, growth hormone, estrogen, ciliary neurotrophic factor (CNTF), fibroblast growth factor (FGF), transforming growth factor alpha (TGFα) and epidermal growth factor (EGF) in an amount sufficient to increase the number of neural stem cells; and   (c) contacting the neural stem cells from step (b) to a factor selected from the group consisting of erythropoietin (EPO), pituitary adenylate cyclase activating polypeptide (PACAP), prolactin, serotonin, bone morphogenetic protein (BMP) and cAMP in an amount sufficient to enhance the production of neuronal precursor cells or glial precursor cells from the neural stem cells;   with the proviso that when the factor in step (b) is EGF or FGF, the factor in step (c) is PACAP or prolactin.   
   
   
       2 . The method of  claim 1  wherein step (b) is performed prior to step (c). 
   
   
       3 . The method of  claim 1  wherein steps (b) and (c) are performed concurrently. 
   
   
       4 . The method of  claim 1  wherein the neural stem cell is not an embryonic cell. 
   
   
       5 . The method of  claim 1  wherein the neural stem cell is an adult neural stem cell. 
   
   
       6 . The method of  claim 1  wherein the neural stem cell is located in a mammal. 
   
   
       7 . The method of  claim 6  wherein the neural stem cell is provided by transplanting neural stem cells into the mammal. 
   
   
       8 . The method of  claim 7  wherein the transplanted neural stem cells have been expanded in culture prior to being transplanted into the mammal. 
   
   
       9 . The method of  claim 7  wherein the transplanted neural stem cells are syngeneic with the mammal. 
   
   
       10 . The method of  claim 6  wherein the neural stem cell is located in the subventricular zone of the forebrain of the mammal. 
   
   
       11 . The method of  claim 6  wherein the mammal is suffering from or suspected of having a neurodegenerative disease or condition. 
   
   
       12 . The method of  claim 11  wherein the disease or condition is brain injury. 
   
   
       13 . The method of  claim 12  wherein the brain injury is a stroke. 
   
   
       14 . The method of  claim 11  wherein the disease or condition is selected from the group consisting of Alzheimer's disease, multiple sclerosis (MS), Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease.