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 method for treating a degenerative intervertebral disc in a patient in need thereof comprising:
 culturing harvested nucleated cells in a culture medium under selective pressure of about 1% to about 10% oxygen for 1-28 days;   obtaining viable mesenchymal stem cells capable of growth in the culture medium under selective pressure of about 1% to about 10% oxygen;   implanting the viable mesenchymal stem cells in a posterior disc annulus of the degenerative intervertebral disc; and   administering a compound in the posterior disc annulus, 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;   wherein the administering a compound is before, during, or after implanting the viable mesenchymal stem cells.   
     
     
         2 . The method of  claim 1  wherein the compound is selected from the group consisting of VEGF-B, TGF-β, FGF, PDGF, HGF, IGF, and combinations thereof. 
     
     
         3 . The method of  claim 1  wherein the compound is selected from the group consisting of TGF-β, FGF, PDGF, IGF, and combinations thereof. 
     
     
         4 . The method of  claim 1  wherein the compound is PDGF. 
     
     
         5 . The method of  claim 1  wherein the compound is FGF. 
     
     
         6 . The method of  claim 1  wherein the compound is VEGF-B. 
     
     
         7 . The method of  claim 1  wherein the compound is TGF-β. 
     
     
         8 . The method of  claim 1  wherein the selective pressure includes culturing the harvested nucleated cells in from about 3 to about 7% oxygen. 
     
     
         9 . The method of  claim 1  wherein the selective pressure further includes culturing the harvested nucleated cells in from about 2 to about 10% carbon dioxide. 
     
     
         10 . The method of  claim 8  wherein the selective pressure further includes culturing the harvested nucleated cells in from about 2 to about 10% carbon dioxide. 
     
     
         11 . The method of  claim 1  wherein the culturing of harvested nucleated cells is performed in a basal culture media made from a D-MEM base. 
     
     
         12 . A method for treating a degenerative intervertebral disc in a patient in need thereof comprising:
 culturing harvested nucleated cells in a culture medium under selective pressure of about 3 to about 10% oxygen for two to five passages;   obtaining viable mesenchymal stem cells capable of growth in the culture medium under selective pressure of about 3% to about 10% oxygen;   providing the viable mesenchymal stem cells for implantation in a posterior disc annulus of the degenerative intervertebral disc; and   providing a compound to be administered in the posterior disc annulus, 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;   wherein the compound is administered before, during, or after implanting the viable mesenchymal stem cells.   
     
     
         13 . The method of  claim 12  wherein the compound is selected from the group consisting of VEGF-B, TGF-β, FGF, PDGF, HGF, IGF, and combinations thereof. 
     
     
         14 . The method of  claim 12  wherein the compound is PDGF. 
     
     
         15 . The method of  claim 12  wherein the compound is FGF. 
     
     
         16 . The method of  claim 12  wherein the compound is VEGF-B. 
     
     
         17 . The method of  claim 12  wherein the compound is TGF-β. 
     
     
         18 . The method of  claim 12  wherein the selective pressure includes culturing the harvested nucleated cells in from about 3 to about 7% oxygen. 
     
     
         19 . The method of  claim 12  wherein the selective pressure further includes culturing the harvested nucleated cells in from about 2 to about 10% carbon dioxide. 
     
     
         20 . A method for treating an avascular zone in a patient in need thereof comprising:
 culturing harvested nucleated cells in a culture medium under selective pressure of about 3% to about 10% oxygen for 1-28 days;   obtaining viable mesenchymal stem cells capable of growth in the culture medium under selective pressure of about 3% to about 10% oxygen;   implanting the viable mesenchymal stem cells in the avascular zone; and   administering a compound in the avascular zone, 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;   wherein the administering a compound is before, during, or after implanting the viable mesenchymal stem cells.