Methods of inducing or enhancing cartilage repair

Abstract

The invention relates to methods of enhancing repair of a cartilage and/or inducing formation of a cartilage by administering a cell, which expresses a factor of the T-box family, which includes inter-alia the brachyury. In another embodiment, the invention relates to an engineered cell, which is transfected with a vector comprising a nucleic acid sequence encoding a factor of the T-box family, thereby expressing a factor of the T-box family. In another embodiment, the invention relates to compositions comprising a vector, which comprises a nucleic acid sequence encoding a factor of the T-box family and in another embodiment the composition-comprising cell that expresses a factor of the T-box family, which includes inter-alia the brachyury.

What is claimed is:  
     
         1 . A method of enhancing repair of a cartilage comprising the step of administering to a subject an effective amount of a cell which expresses at least one factor of the T-box family, thereby enhancing repair of the cartilage.  
     
     
         2 . The method of  claim 1 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         3 . The method of  claim 1 , wherein said factor of the T-box is brachyury.  
     
     
         4 . The method of  claim 1 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         5 . The method of  claim 4 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         6 . A method of inducing formation of a cartilage comprising the step of administering to a subject an effective amount of a cell which expresses at least one factor of the T-box family, thereby inducing formation of the cartilage.  
     
     
         7 . The method of  claim 6 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         8 . The method of  claim 6 , wherein said factor of the T-box is brachyury.  
     
     
         9 . The method of  claim 6 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         10 . The method of  claim 9 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         11 . A method of enhancing repair of a cartilage in the body comprising the step of administrating a recombinant vector which comprises a nucleic acid encoding a factor of the T-box family to the cartilage of a subject, thereby enhancing repair of the cartilage.  
     
     
         12 . The method of  claim 1   1 , wherein said factor of the T-box is brachyury.  
     
     
         13 . The method of  claim 11 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         14 . The method of  claim 13 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         15 . A method of inducing formation of a cartilage in the body comprising the step of administrating a recombinant vector which comprises a nucleic acid encoding a factor of the T-box family to the cartilage of a subject, thereby inducing formation of the cartilage.  
     
     
         16 . The method of  claim 15 , wherein said factor of the T-box is brachyury.  
     
     
         17 . The method of  claim 15 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         18 . The method of  claim 17 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         19 . A method of inducing chondrocyte differentiation comprising the step of administering of a recombinant vector which comprises a nucleic acid encoding a factor of the T-box family, thereby inducing chondrocyte formation.  
     
     
         20 . The method of  claim 19 , wherein said factor of the T-box is brachyury.  
     
     
         21 . The method of  claim 19 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         22 . The method of  claim 19 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         23 . A method of repairing or forming a cartilage in a subject in need comprising the steps of: 
 obtaining a cell from of the subject;    transfecting said cell with a recombinant vector comprising a nucleic acid sequence encoding a factor of the T-box family, so as to obtain an engineered cell which expresses a factor of the T-box family; and    administering said engineered cell to the subject.    
     
     
         24 . The method of  claim 23 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         25 . The method of  claim 23 , wherein said factor of the T-box is brachyury.  
     
     
         26 . The method of  claim 23 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         27 . The method of  claim 26 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         28 . The method of  claim 23 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         29 . The method of  claim 28 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         30 . A method for the production of transplantable cartilage matrix, the method comprising the steps of: 
 obtaining a cell;    transfecting said cell with a recombinant vector comprising a nucleic acid sequence encoding a factor of the T-box family, so as to obtain an engineered cell which expresses a factor of the T-box family; and    culturing said cell with the cell-associated matrix for a time effective for allowing formation of a transplantable cartilage matrix.    
     
     
         31 . The method of  claim 30 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         32 . The method of  claim 30 , wherein said factor of the T-box is brachyury.  
     
     
         33 . The method of  claim 30 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         34 . The method of  claim 33 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         35 . The method of  claim 30 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         36 . The method of  claim 35 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         37 . An engineered cell which expresses a factor of the T-box family.  
     
     
         38 . The cell of  claim 37 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         39 . The cell of  claim 37 , wherein said factor of the T-box is brachyury.  
     
     
         40 . The cell of  claim 37 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         41 . The cell of  claim 40 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         42 . The cell of  claim 37 , wherein said cell is a human mesenchymal cell.  
     
     
         43 . A composition comprising an engineered cell which expresses a factor of the T-box family and a pharmaceutically acceptable carrier.  
     
     
         44 . The composition of  claim 43 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a syniovial cell.  
     
     
         45 . The composition of  claim 43 , wherein said factor of the T-box is brachyury.  
     
     
         46 . The composition of  claim 43 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         47 . The composition of  claim 46 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         48 . The composition of  claim 46 , wherein said composition is a pharmaceutically composition.  
     
     
         49 . A composition comprising at least one recombinant vector which comprises a nucleic acid sequence encoding at least one factor of the T-box family and a pharmaceutically acceptable carrier.  
     
     
         50 . The composition of  claim 49 , wherein said composition is a pharmaceutically composition.  
     
     
         51 . The composition of  claim 49 , wherein said factor of the T-box is brachyury.  
     
     
         52 . The composition of  claim 49 , wherein said method further comprises administering a recombinant vector which comprises a nucleic acid encoding a factor which upregulates the expression of the T-box transcription factor.  
     
     
         53 . The composition of  claim 52 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         54 . An implant device comprising at least one engineered cell which expresses a factor of the T-box family and a pharmaceutically acceptable carrier.  
     
     
         55 . The device of  claim 54 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         56 . The method of  claim 54 , wherein said factor of the T-box is brachyury.  
     
     
         57 . The method of  claim 54 , wherein said cell further expresses factor which upregulates the expression of the T-box transcription factor.  
     
     
         58 . The method of  claim 57 , wherein said factor which upregulates the expression of the factor of the T-box is FGF or BMP2.  
     
     
         59 . The method of  claim 54 , wherein said cell is human cell.  
     
     
         60 . A method of suppressing cartilage formation, comprising the step of administering to a subject in need an antagonist to a factor of the T-box family thereby suppressing cartilage formation.  
     
     
         61 . The method of  claim 60 , wherein said antagonist is an antibody, an antisense, a protein, a nucleic acid or a carbonhydrate.  
     
     
         62 . The method of  claim 60 , wherein said antagonist is a dominant negative factor of the T-box family.  
     
     
         63 . The method of  claim 60 , wherein said antagonist is a dominant negative Brachyury.  
     
     
         64 . A method of screening candidate nucleic acid sequence, which is, involved in the early stages of cartilage development, said methods comprising the step of obtaining a cell; 
 transfecting said cell with a vector comprising a nucleic acid sequence encoding to FGFR3;    obtaining mRNA from said cell;    synthesizing cDNA from said mRNA;    amplifying said cDNA-hybrid, so as to obtain an amplified product;    detecting said amplified product; and    comparing said amplified products from said sample to amplified products derived from known samples thereby identifying candidate nucleic acid sequence which is involved in the early stages of cartilage development.    
     
     
         65 . The cell of  claim 64 , wherein said cell is a mesenchymal stem cell, a progenitor cell, a cell is capable to differentiate into a chondrocyte a fibroblast or a synovial cell.  
     
     
         66 . The cell of  claim 64 , wherein said cell is a human mesenchymal stem cell.