Pouch-like Construct for Preventing Heart Distension

Abstract

The invention is directed to a pouch-like construct comprising mammalian tissue which can be used for preventing distension and/or resisting dilation of the heart in a mammal. Preferably, the pouch-like tissue construct has contractile properties. The invention further relates to a method for the preparation of a pouch-like construct comprising mammalian tissue which can be used for the above purposes.

1 . A method for the preparation of a pouch-like construct suitable for enclosing at least part of a heart of a mammal and comprising engineered tissue, wherein the method comprises the steps of: a) providing a matrix having a recess in one surface of the matrix, which recess has desired dimensions corresponding to desired dimensions of the pouch-like construct's exterior to be formed, b) providing a body having dimensions corresponding to desired dimensions of the pouch-like construct's interior to be formed, c) disposing a body in the recess of the matrix such that the body is spaced from walls of the recess to form a space between the body and the walls of the recess corresponding to the desired dimensions of the construct, d) disposing a reconstitution mixture in the recess, which reconstitution mixture comprises mammalian cells and suitable scaffold material which can be incubated to form an engineered tissue construct, e) contacting the reconstitution mixture disposed within the recess with a culture medium suitable for culturing the cells in the reconstitution mixture, f) incubating the reconstitution mixture until a tissue construct forms within the matrix recess between the body and the matrix, g) removing the body with the tissue construct adherent thereto from the matrix recess, and h) separating the tissue construct from the body. 
     
     
         2 . The method according to  claim 1 , wherein the step of providing a matrix includes providing a porous matrix filled with a liquid in order to impede outflow of the reconstitution mixture from the recess into the porous matrix, and wherein the step of contacting the reconstitution mixture disposed within the recess with a culture medium includes disposing a liquid culture medium on the surface of the matrix in which the recess is formed in order to form a layer of the culture medium on top of the matrix and the reconstitution mixture disposed within the recess. 
     
     
         3 . The method according to  claim 1 , wherein the step of providing a matrix includes providing a porous matrix including the culture medium. 
     
     
         4 . The method according to  claim 1 , wherein the body is spherical. 
     
     
         5 . The method according to any of the preceding  claim 1 , wherein the body comprises a surface of glass, teflon or silicone. 
     
     
         6 . The method according to  claim 1 , wherein the body is an inflatable structure. 
     
     
         7 . The method according to  claim 1 , wherein step c) is performed prior to step d). 
     
     
         8 . The method according to  claim 1 , wherein step d) is performed prior to step c). 
     
     
         9 . The method according to  claim 1 , wherein after step h), the construct is subjected to tensile stress. 
     
     
         10 . The method according to  claim 9 , wherein the tensile stress is static, phasic or auxotonic stress or a combination thereof. 
     
     
         11 . The method according to  claim 10 , wherein the tensile stress is auxotonic stress. 
     
     
         12 . A pouch-like construct obtainable by the method according to  claim 1 . 
     
     
         13 . A pouch-like construct suitable for enclosing at least part of a heart of a mammal, wherein the pouch-like construct comprises mammalian tissue. 
     
     
         14 . The pouch-like construct according to  claim 13 , wherein the pouch-like construct consists of mammalian tissue. 
     
     
         15 . The pouch-like construct according to  claim 13 , wherein the mammalian tissue comprises cardiac myocytes. 
     
     
         16 . The pouch-like construct according to  claim 15 , wherein more than 25% of volume of the construct consists of cardiac myocytes. 
     
     
         17 . The pouch-like construct according to  claim 16 , wherein the construct has contractile properties. 
     
     
         18 . The pouch-like Pouch like construct according to  claim 13 , wherein the mammalian tissue is human heart tissue comprising human cardiac myocytes. 
     
     
         19 . The pouch-like construct according to  claim 18 , wherein the construct has a wall thickness of 1-8 mm. 
     
     
         20 . The pouch-like construct according to  claim 19 , wherein the construct has a wall thickness of 2-3 mm.