In vitro model for neuronal death

Abstract

This invention demonstrates the formation of a novel polarized membrane lipid raft signaling module in neurons, in response to several diverse neurotoxic stimuli. This polarization occurs well before neurons commit to die, and is an early mechanism in death signaling. The formation of this signaling module is dependent on cholesterol for its formation and provides a mechanistic explanation for the protective effects of cholesterol depleting drugs in several non-neural models of cell death. As such, the formation of the signaling module lends itself as a novel screen for the identification of new drugs and therapeutics which would retard its formation and protect against neuronal injury and death.

The invention claimed is: 
     
         1 . A method of treating a disease in a subject in need thereof, the method comprising administering to said subject a population of cholesterol-depleted mammalian stem cells in vitro, produced by the process comprising:
 (a) culturing a starting population comprising mammalian stem cells in a cell culture medium;   (b) amplifying and/or enriching for said cholesterol-depleted mammalian stem cells by adding at least about 0.1% cyclodextrin to the cell culture medium in which said starting population is cultured.   
     
     
         2 . The method of  claim 1 , wherein the disease is neurodegeneration, stroke, or trauma. 
     
     
         3 . The method of  claim 1 , wherein the disease is selected from Alzheimer's disease and Parkinson's disease. 
     
     
         4 . The method of  claim 1 , wherein the cyclodextrin is gamma cyclodextrin. 
     
     
         5 . The method of  claim 1 , wherein the cyclodextrin is methyl-β-cyclodextrin. 
     
     
         6 . The method of  claim 1 , wherein the stem cells are human cells. 
     
     
         7 . The method of  claim 1 , wherein the stem cells are CD34 +  human stem cells.