Three-dimensional tissue structure

Abstract

The present invention provides a prosthetic tissue or sheet capable of withstanding implantation operations, which can be used in actual operation and can be produced by culture. The present invention also provides a novel therapy which can substitute for cell therapy. Particularly, the present invention provides a method for producing a prosthetic tissue comprising a cell derived from a part other than myocardium and capable of withstanding implantation operation. The above-described objects of the present invention were partially achieved by finding that by culturing cells under specific culture conditions, the cells are unexpectedly organized into a tissue, and the resultant prosthetic tissue is capable of being detached from culture dishes. The present invention also provides a three-dimensional structure applicable to heart, comprising a cell derived from a part other than the myocardium of an adult.

We claim: 
     
         1 . A three-dimensional structure applicable to heart, comprising myoblasts. 
     
     
         2 . The structure according to  claim 1 , wherein the structure is free from scaffold. 
     
     
         3 . The structure according to  claim 1 , wherein the myoblasts are derived from a subject and the structure is applicable to the subject. 
     
     
         4 . The structure according to  claim 1 , wherein the myoblasts are not derived from a subject and the structure is applicable to the subject. 
     
     
         5 . The structure according to  claim 1 , wherein the myoblasts are skeletal myoblasts. 
     
     
         6 . The structure according to  claim 1 , comprising a monolayer cell sheet of myoblasts. 
     
     
         7 . The structure according to  claim 1 , comprising a multilayer cell sheet of myoblasts. 
     
     
         8 . The structure according to  claim 7 , wherein the multilayer cell sheet has biological connection between cell sheets, wherein the biological connection is selected from the group consisting of connection via extracellular matrix, electrical connection, and connection without scaffold. 
     
     
         9 . The structure according to  claim 1 , wherein the structure expresses at least one non-adult heart marker selected from the group consisting of myosin heavy chain IIa, myosin heavy chain IIb, myosin heavy chain IId(IIx), CD56, MyoD, Myf5, and myogenin. 
     
     
         10 . The structure according to  claim 1 , which is obtainable by the process comprising:
 culturing myoblasts on a cell culture support grafted with a temperature responsive macromolecule having an upper limit critical solution temperature or lower limit critical solution temperature in an aqueous solution of from 0° C. to 80° C. to form a cell sheet;   setting a culture medium temperature to the upper limit critical solution temperature or more or the lower limit critical solution temperature or less; and   detaching the cultured cell as the three-dimensional structure.   
     
     
         11 . A method for treating heart disease, comprising transplanting the structure according to  claim 1  to a heart of a subject suffering from the disease. 
     
     
         12 . The method according to  claim 11 , wherein the heart disease is selected from the group consisting of heart failure, ischemic heart disease, myocardial infarct, cardiomyopathy, myocarditis, hypertrophic cardiomyopathy, dilated phase hypertrophic cardiomyopathy, and dilated cardiomyopathy. 
     
     
         13 . A method for producing a three-dimensional structure comprising:
 culturing cells derived from the part other than myocardium of an adult on a cell culture support grafted with a temperature responsive macromolecule having an upper limit critical solution temperature or lower limit critical solution temperature in an aqueous solution of from 0° C. to 80° C. to form a cell sheet, wherein the cells derived from the part other than myocardium of an adult are myoblasts or embryonic stem cells;   setting a culture medium temperature to the upper limit critical solution temperature or more or the lower limit critical solution temperature or less; and   detaching the cultured cell as the three-dimensional structure.   
     
     
         14 . The method according to  claim 13 , wherein the cells derived from the part other than myocardium of an adult are embryonic stem cells, and wherein the stem cells differentiate into cardiomyocytes and form a cell sheet of cardiomyocytes. 
     
     
         15 . The method according to  claim 13 , wherein a treatment using a protein degrading enzyme is not performed in or before the detaching step.