Methods and compositions for modulation of migration of neurogenic cells

Abstract

Disclosed herein are methods for the treatment of traumatic brain injury by transplantation of cells descended from marrow adherent stem cells that express an exogenous Notch intracellular domain. The transplanted cells form a pathway along which endogenous neurogenic cells proliferate and migrate from the subventricular zone to the site of injury.

We claim: 
     
         1 . A method for inducing migration of neurogenic cells from a neurogenic niche to a site of brain injury in a subject, the method comprising:
 introducing cells into the brain between the neurogenic niche and the site of brain injury, wherein said cells are obtained by a method comprising:   (a) providing a culture of marrow adherent stem cells (MSCs);   (b) contacting the culture of (a) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD);   (c) selecting cells that comprise the polynucleotide of (b);   (d) withdrawing selection; and   (e) further culturing the cells in the absence of selection.   
     
     
         2 . The method of  claim 1 , wherein the brain injury is a traumatic brain injury. 
     
     
         3 . The method of  claim 2 , wherein the traumatic brain injury results from external mechanical force. 
     
     
         4 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         5 . The method of  claim 4 , wherein the subject is a human. 
     
     
         6 . The method of  claim 1 , wherein the neurogenic niche is the subventricular zone. 
     
     
         7 . The method of  claim 1 , wherein the site of brain injury is in the cortex. 
     
     
         8 . The method of  claim 1 , wherein the MSCs are obtained from a human. 
     
     
         9 . A method for inducing proliferation of neurogenic cells in the brain of a subject, the method comprising:
 introducing cells into the brain between a neurogenic niche and a site of brain injury, wherein said cells are obtained by a method comprising:   (a) providing a culture of marrow adherent stem cells (MSCs);   (b) contacting the culture of (a) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD);   (c) selecting cells that comprise the polynucleotide of (b);   (d) withdrawing selection; and   (e) further culturing the cells in the absence of selection.   
     
     
         10 . The method of  claim 9 , wherein the subject has a traumatic brain injury. 
     
     
         11 . The method of  claim 10 , wherein the traumatic brain injury results from external mechanical force. 
     
     
         12 . The method of  claim 9 , wherein the subject is a mammal. 
     
     
         13 . The method of  claim 12 , wherein the subject is a human. 
     
     
         14 . The method of  claim 9 , wherein the neurogenic cells reside in the subventricular zone. 
     
     
         15 . The method of  claim 9 , wherein the neurogenic cells migrate to the cortex. 
     
     
         16 . The method of  claim 1 , wherein the MSCs are obtained from a human.