Enhancing cell migration by increasing telomerase activity

Abstract

It has been discovered that increasing telomerase activity in cells surrounding a wound promotes wound healing. Replication capacity is enhanced, and the mobility of the epithelial cells can be increased by 3-fold or more. Particular aspects of the invention described in this disclosure include the use of agents that increase telomerase activity in cells at the site of the wound, promoting cells to move to the site and restore an epithelial layer and the underlying stratum.

1 . A method for enhancing migration of a cell on a solid surface, comprising contacting the cell with a means for increasing telomerase enzyme activity in the cell.  
     
     
         2 . The method of  claim 1 , comprising increasing expression of telomerase reverse transcriptase (TERT) in the cell.  
     
     
         3 . The method of  claim 2 , comprising transfecting the cells in vitro with an expression vector encoding TERT.  
     
     
         4 . The method of  claim 3 , wherein the vector is an adenovirus vector.  
     
     
         5 . A method for enhancing migration of epithelial cells, comprising increasing telomerase enzyme activity in the cells.  
     
     
         6 . The method of  claim 5 , comprising increasing expression of telomerase reverse transcriptase (TERT) in the cells.  
     
     
         7 . The method of  claim 6 , comprising transfecting the cells with an expression vector encoding human TERT.  
     
     
         8 . The method of  claim 5 , wherein the cells are keratinocytes.  
     
     
         9 . The method of  claim 5 , wherein the epithelial cells express at least 2 TPG units of telomerase activity as measured in a telomeric repeat amplification protocol (TRAP) assay.  
     
     
         10 . The method of  claim 5 , whereby the epithelial cells migrate on a solid surface at a rate of at least two cell diameters per day.  
     
     
         11 . The method of  claim 5 , whereby the rate of migration of epithelial cells across a wound site is increased.  
     
     
         12 . A method for enhancing migration of epithelial cells in vivo, comprising transfecting the cells with an expression vector encoding TERT.  
     
     
         13 . The method of  claim 12 , which is a method for treating a wound in which the rate of migration of epithelial cells across a wound site is increased.  
     
     
         14 . The method of  claim 13 , comprising administering a pharmaceutical composition comprising an adenovirus expression vector encoding TERT at or around the would site.  
     
     
         15 . The method of  claim 13 , wherein the wound is a skin wound.  
     
     
         16 . The method of  claim 13 , wherein the composition further comprises a means for retaining the adenovirus vector at or around the wound site.