Blood vessel formation from endothelial colony forming cells

Abstract

Methods and compositions to form fully functional blood vessels in vivo using endothelial colony forming cells (ECFCs) are disclosed. Culturing ECFCs in a support material results in association of ECFCs in vitro and formation of blood vessels in vivo upon implantation. Direct administration of cultured ECFCs form blood vessels in vivo. Formation of blood vessels is useful in treating a variety of medical conditions including ischemia and hypoxia.

1 . A method for forming a functional vasculature in vivo in a host, the method comprising: 
 (a) culturing a plurality of isolated high proliferative-potential endothelial colony forming cells (HPP-ECFC) in a support material;    (b) implanting the support material comprising the endothelial colony forming cells to a target site; and    (c) forming the functional vasculature in vivo in the target site in the host.    
   
   
       2 . The method of  claim 1 , wherein the support material is an artificial matrix.  
   
   
       3 . The method of  claim 2 , wherein the matrix is a gel comprising one or more components selected from the group consisting of collagen, fibronectin, gelatin, laminin and any extracellular matrix constituent.  
   
   
       4 . The method of  claim 1 , wherein the ECFCs are circulating ECFCs.  
   
   
       5 . The method of  claim 1 , wherein the target site comprises an ischemic injury.  
   
   
       6 . The method of  claim 1 , wherein the target site is selected from the group consisting of heart, lungs, kidney, liver, and pancreas.  
   
   
       7 . The method of  claim 1 , wherein the host is a human.  
   
   
       8 . The method of  claim 1 , wherein the target site requires vessel formation.  
   
   
       9 . The method of  claim 1 , wherein the endothelial colony forming cells comprise a density of about 1-2 million cells per milliliter volume of implantation support material.  
   
   
       10 . The method of  claim 1 , wherein the endothelial colony forming cells are cultured for about 12-48 hours prior to implantation.  
   
   
       11 . The method of  claim 1 , wherein the support material is viscous.  
   
   
       12 . The method of  claim 1 , wherein the support material provides three-dimensional cell growth.  
   
   
       13 . The method of  claim 1 , wherein the support material comprising the cells is administered directly to the target site.  
   
   
       14 . A method for forming functional blood vessels in vivo in a host, the method comprising: 
 (a) culturing cord blood endothelial colony forming cells (ECFCs) in vitro;    (b) administering the cultured cells to a target site; and    (c) forming the vasculature in vivo in the host.    
   
   
       15 . An implantable scaffold for treating an ischemic injury in a host, the scaffold comprising high proliferative-potential endothelial colony forming cells (HPP-ECFC), wherein the endothelial colony forming cells associate to form blood vessels in vivo.  
   
   
       16 . The scaffold of  claim 15  comprising a growth factor.  
   
   
       17 . An engineered tissue comprising a biologically compatible support material and a plurality of cultured high proliferative-potential endothelial colony forming cells (HPP-ECFC) that initiate vessel formation.  
   
   
       18 . A composition comprising an effective amount of high proliferative-potential endothelial colony forming cells (HPP-ECFC) culture on a biocompatible gel material.  
   
   
       19 . The composition of  claim 19  comprises one or more components of an extra cellular matrix.  
   
   
       20 . The composition of  claim 19 , wherein the ECFCs are cultured on a growth medium for endothelial cells.