Method for producing tissue and organ

Abstract

The present invention provides a means for reconstituting tissues and organs having mature functions. A method of preparing a tissue or an organ, comprising coculturing an organ cell with a vascular endothelial cell and a mesenchymal cell, generating an organ bud, transplanting the organ bud into a non-human animal, and then isolating from the non-human animal the transplanted organ bud-derived tissue or organ.

1 . A method of preparing an organ bud, comprising:
 culturing a vascular endothelial cell and an organ cell together with at least one cell and/or factor selected from the group consisting of mesenchymal cells, factors secreted from vascular endothelial cells, factors secreted from mesenchymal cells, and factors secreted as a result of the presence of both vascular endothelial cells and mesenchymal cells with no use of a scaffolding for a time sufficient to form an organ bud, wherein the organ bud is a structure capable of differentiating into an organ through maturing.   
     
     
         2 . The method of  claim 1 , wherein the organ cell is a differentiated cell. 
     
     
         3 . The method of  claim 1 , wherein the organ cell is an undifferentiated cell. 
     
     
         4 . The method of  claim 1 , wherein the organ cell is a cell of an endodermal organ or a cell capable of differentiating thereinto, a cell of a mesodermal organ or a cell capable of differentiating thereinto, or a cell of an ectodermal organ or a cell capable of differentiating thereinto. 
     
     
         5 . The method of  claim 4 , wherein the organ cell is a cell of an endodermal organ or a cell capable of differentiating thereinto. 
     
     
         6 . The method of  claim 5 , wherein the endodermal organ is liver or pancreas. 
     
     
         7 . The method of  claim 1 , wherein the organ cell is an induced pluripotent stem cell-derived cell. 
     
     
         8 . The method of  claim 7 , wherein the induced pluripotent stem cell is derived from human. 
     
     
         9 . The method of  claim 1 , wherein the vascular endothelial cell and organ cell are cultured with no use of a scaffolding in a medium for culturing vascular endothelial cells, together with at least one cell and/or factor selected from the group consisting of mesenchymal cells, factors secreted from vascular endothelial cells, factors secreted from mesenchymal cells, and factors secreted as a result of the presence of both vascular endothelial cells and mesenchymal cells to form an organ bud. 
     
     
         10 . The method of  claim 1 , wherein the vascular endothelial cell and organ cell are plated on a gel and cultured together with at least one cell and/or factor selected from the group consisting of mesenchymal cells, factors secreted from vascular endothelial cells, factors secreted from mesenchymal cells, and factors secreted as a result of the presence of both vascular endothelial cells and mesenchymal cells. 
     
     
         11 . The method of  claim 1 , wherein the vascular endothelial cell is a differentiated cell. 
     
     
         12 . The method of  claim 1 , wherein the vascular endothelial cell is an undifferentiated cell. 
     
     
         13 . The method of  claim 1 , wherein the mesenchymal cell is a differentiated cell. 
     
     
         14 . The method of  claim 1 , wherein the mesenchymal cell is an undifferentiated cell. 
     
     
         15 . A method of preparing a tissue or an organ, comprising transplanting the organ bud prepared by the method of  claim 1  into a non-human animal and differentiating the organ bud into a tissue or an organ. 
     
     
         16 . A method of transplanting an organ bud, comprising transplanting the organ bud prepared by the method of  claim 1  into a human or a non-human animal. 
     
     
         17 . The method of  claim 16 , wherein the site of transplantation of the organ bud is selected from the group consisting of the intracranial space, the mesenteric space, the liver, the spleen, the kidney, the kidney subcapsular space, and the supraportal space. 
     
     
         18 . A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the organ bud prepared by the method of  claim 1  into a human or a non-human animal and differentiating the organ bud into a tissue or an organ. 
     
     
         19 . A method of preparing a non-human chimeric animal, comprising transplanting the organ bud prepared by the method of  claim 1  into a non-human animal and differentiating the organ bud into a tissue or an organ. 
     
     
         20 . A method of evaluating a drug, comprising using at least one member selected from the group consisting of the organ bud prepared by the method of  claim 1 , the tissue or organ, and the non-human chimeric animal. 
     
     
         21 . A method of evaluating a drug, comprising using at least one member selected from the group consisting of the organ bud, the tissue or organ prepared by the method of  claim 15 , and the non-human chimeric animal. 
     
     
         22 . A method of evaluating a drug, comprising using at least one member selected from the group consisting of the organ bud, the tissue or organ, and the non-human chimeric animal prepared by the method of  claim 19 .