Methods, systems, and compositions for neuronal differentiation of multipotent stromal cells

Abstract

Some embodiments of the invention comprise methods, systems, and compositions to selectively induce, whether in vitro or in vivo, the neuronal differentiation of multipotent stromal cells through the application of microRNAs, including but not limited to miRNA-124, miRNA-137 and/or miRNA-9* expression products of those miRNAs, and molecules and compositions containing functional elements of those miRNAs. Some embodiments of the invention also comprise the therapeutic administration and use of such induced cells to treat mammalian injuries and diseases, including but not limited to, nervous system injuries or diseases that may otherwise result in decreased cell or system function.

What is claimed is: 
     
         1 . A method of trans-differentiating mammalian multipotent stromal cells into neuronal stem cells, the method comprising the steps of:
 a) providing a population of mammalian multipotent stromal cells; and   b) expressing microRNA-124 in the population of mammalian multipotent stromal cells so as to generate a population of neuronal stem cells expressing nestin,   thereby trans-differentiating mammalian multipotent stromal cells into neuronal stem cells.   
     
     
         2 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         3 . The method of  claim 1 , further comprising step (c) comprising analyzing a marker in said population of neuronal stem cells, wherein said marker comprises a neuronal morphology. 
     
     
         4 . The method of  claim 1 , wherein said mammalian multipotent stromal cells are derived from a tissue selected from the group consisting of adipose tissue, umbilical cord tissue, bone marrow tissue and placenta tissue. 
     
     
         5 . The method of  claim 1 , further comprising expressing in said mammalian multipotent stromal cells glial derived neurotrophic factor (GDNF). 
     
     
         6 . The method of  claim 1 , further comprising expressing in said mammalian multipotent stromal cells microRNA-137, microRNA-9* or both. 
     
     
         7 . The method of  claim 1 , wherein said expressing comprises transfection, overexpression of exogenous miRNA or transduction of pre-miRNA. 
     
     
         8 . A method of treating a mammal suffering from nervous system injury or disease, comprising:
 a. performing the method of  claim 1 ; and   b. administering said trans-differentiated mammalian multipotent stromal cells, secreted factors therefrom or both to said mammal;   thereby treating a mammal suffering from nervous system injury or disease.   
     
     
         9 . The method of  claim 8 , wherein said mammal is a human. 
     
     
         10 . The method of  claim 8 , further comprising expressing in said mammalian multipotent stromal cells microRNA-137, microRNA-9* or both. 
     
     
         11 . The method of  claim 8 , wherein said nervous system injury is a spinal injury. 
     
     
         12 . The method of  claim 8 , wherein said nervous system disease is a neurodegenerative disorder. 
     
     
         13 . The method of  claim 11 , wherein said neurodegenerative disorder is selected from amyotrophic lateral sclerosis, and multiple sclerosis. 
     
     
         14 . The method of  claim 11 , wherein said neurodegenerative disorder is a motor neuron disease.