Method of obtaining terminally differentiated neuronal lineages and uses thereof

Abstract

Provided is a method of inducing transdifferentiation of mesenchymal stem cells (MSC), the method including (a) culturing MSC in a first culture medium including a growth factor selected for allowing formation of neuralized MSC (NMSC); (b) allowing the NMSC to proliferate for a sufficient time during which said culture medium is renewed at least once; and (c) culturing the NMSC of (b) in a second culture media including cerebrospinal fluid (CSF) for a time sufficient for the NMSC to differentiate into a population of cells including terminally differentiated neurons, astrocytes and oligodendrocytes. Also provided by the present invention is the use of MSC or NMSC for providing a composition including said population and to kits including MSC or NMSC and instructions for use of same.

1 .- 24 . (canceled) 
     
     
         25 . A composition comprising a population of cells comprising terminally differentiated neurons, astrocytes and oligodendrocytes, wherein said population of cells is characterized by at least 10% expression GFAP and of Tubulin-beta-III, at least 10% expression of MAP2 and of S100 and at least a 10% expression of GalC and of CNPase. 
     
     
         26 . The composition of  claim 25 , wherein said population is characterized by at least 65% expression GFAP and of Tubulin-beta-III, at least a 35% expression of MAP2 and of S100, at least 10% expression of GalC and of CNPase. 
     
     
         27 . The composition of  claim 25 , wherein said population is characterized by expression of MAP2 in an amount of 75-85%, Tubulin-beta-III in an amount of 68-77%, GFAP in an amount of 45-55%, S100 in an amount of 35-45%, GalC in an amount of 15-20% and CNPase in an amount of 10-18%. 
     
     
         28 . The composition of  claim 25 , wherein said population comprises about 80% neurons, about 15% astrocytes, and about 5% oligodendrocytes. 
     
     
         29 . The composition of  claim 25 , wherein said population of cells is characterized by secretion of NGF or BDNF to a level greater than level of expression of same by naïve mesenchymal stem cells. 
     
     
         30 . The composition of  claim 25 , wherein said population of cells comprises mesenchymal stem cells (MSC)-derived cells. 
     
     
         31 . The method of  claim 25 , wherein said population of cells is derived from neutralized MSC (NMSC). 
     
     
         32 . The composition of  claim 25 , wherein said population of cells is obtainable by a method comprising culturing NMSC cells in a culture media comprising cerebrospinal fluid (CSF) for a time sufficient for the NMSC to differentiate into a population of cells comprising terminally differentiated neurons, astrocytes and oligodendrocytes. 
     
     
         33 . A method of treatment comprising administering to a subject in need of treatment a composition comprising a population of cells comprising terminally differentiated neurons, astrocytes and oligodendrocytes, wherein said population of cells is characterized by at least 10% expression GFAP and of Tubulin-beta-III, at least 10% expression of MAP2 and of S100 and at least a 10% expression of GalC and of CNPase. 
     
     
         34 . The method of  claim 33 , wherein said population is characterized by at least 65% expression GFAP and of Tubulin-beta-III, at least a 35% expression of MAP2 and of S100, at least 10% expression of GalC and of CNPase. 
     
     
         35 . The method of  claim 33 , for treatment of a pathological condition of the nervous system. 
     
     
         36 . The method of  claim 34 , for treatment of a pathological condition of the nervous system. 
     
     
         37 . The method of  claim 35 , wherein the pathological condition of the nervous system is a neurodegenerative disease or a spinal cord injury. 
     
     
         38 . The method of  claim 36 , wherein the pathological condition of the nervous system is a neurodegenerative disease or a spinal cord injury. 
     
     
         39 . The method of  claim 35 , wherein the pathological condition of the nervous system is multiple sclerosis. 
     
     
         40 . The method of  claim 36 , wherein the pathological condition of the nervous system is multiple sclerosis.