Methods of generating oligodendrocytes and cell populations comprising same

Abstract

A method of generating a population of cells useful for treating a brain disorder in a subject is disclosed. The method comprises contacting mesenchymal stem cells (MSCs) with at least one exogenous miRNA having a nucleic acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID NOs: 15-19 and 27-35, thereby generating a population of cells and/or generating neurotrophic factors that may provide important signals to damaged tissues or locally residing stem cells. MSCs differentiated by miRs may also secrete miRs and deliver them to adjacent cells and therefore provide important signals to neighboring endogenous normal or malignant cells.

The invention claimed is: 
     
       1. A method of treating a brain tumor in a subject in need thereof, the method comprising transplanting a therapeutically effective amount of mesenchymal stem cells, or their exosomes, which have been modified to express exogenous miRNA miR-124, wherein said mesenchymal stem cells or exosomes deliver said exogenous miRNA to the cytosol of a cell of the tumor, thereby treating the brain tumor. 
     
     
       2. The method of  claim 1 , wherein said brain tumor is a glioma. 
     
     
       3. The method of  claim 1 , wherein said brain tumor is an oligodendroglioma, astrocytoma, meningioma or a metastasis to the brain. 
     
     
       4. The method of  claim 1 , further comprising expressing in said mesenchymal stem cells, or their exosomes, a pro-apoptotic agent. 
     
     
       5. The method of  claim 4 , wherein said pro-apoptotic agent comprises soluble or membranal TNF-related apoptosis-inducing ligand (sTRAIL or mTRAIL). 
     
     
       6. The method of  claim 4 , wherein said pro-apoptotic agent comprises membranal CD40 ligand (CD40L). 
     
     
       7. The method of  claim 1 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       8. The method of  claim 1 , wherein said mesenchymal stem cells are derived from the placenta or umbilical cord. 
     
     
       9. The method of  claim 1 , wherein said transplanting is performed intranasally. 
     
     
       10. The method of  claim 4 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       11. The method of  claim 5 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       12. The method of  claim 6 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       13. The method of  claim 1 , further comprising expressing in said mesenchymal stem cells, or their exosomes, at least one of miR-137 and miR-145. 
     
     
       14. The method of  claim 13 , further comprising expressing in said mesenchymal stem cells, or their exosomes, at least one of sTRAIL, and mTRAIL. 
     
     
       15. The method of  claim 13 , further comprising expressing in said mesenchymal stem cells, or their exosomes, membranal CD40L. 
     
     
       16. The method of  claim 14 , further comprising expressing in said mesenchymal stem cells, or their exosomes, membranal CD40L. 
     
     
       17. The method of  claim 13 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       18. The method of  claim 14 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       19. The method of  claim 15 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor. 
     
     
       20. The method of  claim 16 , further comprising irradiating said mesenchymal stem cells, their exosomes, or said cell of a tumor.