Methods and compositions to facilitate repair of avascular tissue

Abstract

Compositions and methods are provided for repairing damaged avascular zones, including intervertebral disc, in a patient in need thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising:
 mesenchymal stem cells cultured under selective pressure of about 1% to about 10% oxygen;   a growth factor; and   a pharmaceutical carrier or diluent.   
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the growth factor is selected from the group consisting of TGF-β, FGF, PDGF, IGF, VEGF-B, and combinations thereof. 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein the growth factor is PDGF. 
     
     
         4 . The pharmaceutical composition of  claim 1  wherein the growth factor is FGF. 
     
     
         5 . The pharmaceutical composition of  claim 1  wherein the growth factor is VEGF-B. 
     
     
         6 . The pharmaceutical composition of  claim 1  wherein the growth factor is TGF-β. 
     
     
         7 . The pharmaceutical composition of  claim 1  wherein the mesenchymal stem cells are cultured under selective pressure of about 1% to about 10% and from about 2 to about 10% carbon dioxide. 
     
     
         8 . The pharmaceutical composition of  claim 1  wherein the mesenchymal stem cells are cultured under selective pressure of about 3% to about 7% oxygen. 
     
     
         9 . The pharmaceutical composition of  claim 8  wherein the mesenchymal stem cells are cultured under selective pressure of about 3% to about 7% and from about 2 to about 10% carbon dioxide. 
     
     
         10 . A pharmaceutical composition comprising:
 mesenchymal stem cells cultured under selective pressure of about 1% to about 10% oxygen;   platelets;   a growth factor; and   a pharmaceutical carrier or diluent.   
     
     
         11 . The pharmaceutical composition of  claim 10  wherein the platelets are treated with thrombin and calcium chloride for 1-7 days. 
     
     
         12 . The pharmaceutical composition of  claim 10  wherein the platelets are treated with thrombin, calcium chloride or its salts, thromboxane A2, adenosine triphosphate and arachidonate. 
     
     
         13 . The pharmaceutical composition of  claim 10  wherein the growth factor is PDGF. 
     
     
         14 . The pharmaceutical composition of  claim 10  wherein the growth factor is FGF. 
     
     
         15 . The pharmaceutical composition of  claim 10  wherein the growth factor is VEGF-B. 
     
     
         16 . The pharmaceutical composition of  claim 10  wherein the growth factor is TGF-β. 
     
     
         17 . The pharmaceutical composition of  claim 10  wherein the mesenchymal stem cells are cultured under selective pressure of about 1% to about 10% and from about 2 to about 10% carbon dioxide. 
     
     
         18 . A pharmaceutical composition comprising:
 mesenchymal stem cells cultured under selective pressure of about 1% to about 10% oxygen;   a compound; and   a pharmaceutical carrier or diluent.   
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the compound is selected from the group consisting of growth factors, cytokines, integrins, cadherins, molecules or drugs that promote angiogenesis, molecules or drugs that promote vasculogenesis, and molecules or drugs that promote arteriogenesis. 
     
     
         20 . The pharmaceutical composition of  claim 18  wherein the compound is selected from the group consisting of VEGF-A, PIGF, VEGF-B, VEGF-C, VEGF-D, TGF-β, Ang-1, Ang-2, IGF, HGF, FGF, Tie2, PDGF, CCL2, Alpha-V Beta-5, Alpha-5 Beta-1, VE-cadherin, PECAM-1, plasminogen activator, nitrogen oxide synthase, and combinations thereof.