Tissue Engineering of Lung

Abstract

The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.

What is claimed: 
     
         1 . A decellularized tissue capable of supporting cell growth, wherein the decellularized tissue exhibits a characteristic of a corresponding natural tissue prior to decellularization. 
     
     
         2 . The decellularized tissue of  claim 1 , wherein said tissue is lung. 
     
     
         3 . The decellularized tissue of  claim 1 , wherein the decellularized tissue exhibits a morphology substantially similar to that of an otherwise identical tissue prior to decellularization. 
     
     
         4 . The decellularized tissue of  claim 1  retaining an extracellular matrix of said corresponding natural tissue, wherein said extracellular matrix comprises an exterior surface, and wherein said exterior surface is substantially intact. 
     
     
         5 . The decellularized tissue of  claim 1 , wherein immunogenic markers have been substantially removed. 
     
     
         6 . The decellularized tissue of  claim 1  exhibiting mechanical properties substantially similar to that of said corresponding natural tissue. 
     
     
         7 . A composition comprising a three dimensional scaffold and a population of cells, wherein said composition is capable of supporting and maintaining the differentiation state of a lung cell. 
     
     
         8 . The composition of  claim 7 , wherein said three dimensional scaffold is a decellularized tissue. 
     
     
         9 . The composition of  claim 7 , wherein the composition exhibits an intact airway tree and vascular network. 
     
     
         10 . The composition of  claim 7 , wherein said population comprises a stein cell. 
     
     
         11 . The composition of  claim 7 , wherein said population comprises epithelial and endothelial cells. 
     
     
         12 . The composition of  claim 7 , wherein said cells are genetically modified. 
     
     
         13 . The composition of  claim 7 , wherein said composition is capable of supporting and maintaining the differentiation state of an alveolar epithelial cell. 
     
     
         14 . The composition of  claim 7 , wherein said scaffold comprises a biocompatable material selected from the group consisting of fibronectin, laminin, collagen, glycoprotein, thrombospondin, elastin, fibrillin, mucopolysaccharide, glycolipid, heparin sulfate, chondroitin sulfate, keratin sulfate, glycosaminoglycan, hyaluronic acid, proteoglycan, vitronectin, poly-D-lysine, polysaccharide, and combinations thereof. 
     
     
         15 . The composition of  claim 7 , comprising cells that exhibit gene expression associated with induction of branching morphogenesis. 
     
     
         16 . The composition of  claim 7 , wherein said gene is CFTR. 
     
     
         17 . The composition of  claim 7 , comprising a characteristic of a lung tissue, wherein said characteristic is selected from the group consisting of branching morphogenesis, distal lung epithelial cytodifferentiation, epithelial growth, vascular development, and combinations thereof. 
     
     
         18 . A method of making an engineered three dimensional tissue capable of supporting and maintaining the differentiation state of a lung cell, said method comprising seeding a decellularized scaffold with a population of cells to produce a seeded scaffold. 
     
     
         19 . The method of  claim 18 , wherein said decellularized scaffold exhibits an intact airway tree and vascular network. 
     
     
         20 . The method of  claim 18 , wherein said population comprises a stem cell. 
     
     
         21 . The method of  claim 18 , wherein said population comprises epithelial and endothelial cells. 
     
     
         22 . The method of  claim 18 , wherein said cells are genetically modified. 
     
     
         23 . The method of  claim 18 , wherein said decellularized scaffold is capable of supporting and maintaining the differentiation state of an alveolar epithelial cell. 
     
     
         24 . The method of  claim 18 , wherein said scaffold comprises a biocompatable material selected from the group consisting of fibronectin, laminin, collagen, glycoprotein, thrombospondin, elastin, fibrillin, mucopolysaccharide, glycolipid, heparin sulfate, chondroitin sulfate, keratin sulfate, glycosaminoglycan, hyaluronic acid, proteoglycan, vitronectin, poly-D-lysine, polysaccharide, and combinations thereof. 
     
     
         25 . The method of  claim 18 , comprising cells that exhibit gene expression associated with induction of branching morphogenesis. 
     
     
         26 . The method of  claim 18 , wherein said gene is CFTR. 
     
     
         27 . The method of  claim 18 , wherein said engineered three dimensional tissue exhibits a characteristic of a lung tissue, wherein said characteristic is selected from the group consisting of branching morphogenesis, distal lung epithelial cytodifferentiation, epithelial growth, vascular development, and combinations thereof. 
     
     
         28 . An in vitro method for screening a test agent for the ability of said test agent to modulate the health of a lung tissue, said method comprising contacting said test agent to an engineered three dimensional lung tissue model and measuring the effect said test agent has on said model, wherein any alteration to the model is an indication that said test agent is able to modulate the health of a lung tissue. 
     
     
         29 . The method of  claim 28 , wherein said engineered three dimensional tissue is derived from a decellularized scaffold. 
     
     
         30 . The method of  claim 28 , wherein the test agent is selected from the group consisting of a chemical agent, a pharmaceutical, a peptide, a nucleic acid, and radiation. 
     
     
         31 . The method of  claim 28 , wherein the test agent is a delivery vehicle for a therapeutic agent. 
     
     
         32 . The method of  claim 28  comprising determining the effect of the test agent on cell number, area, volume, shape, morphology, marker expression or chromosomal fragmentation. 
     
     
         33 . The method of  claim 28 , further comprising the step of selecting an agent which has a desired effect on the lung tissue model. 
     
     
         34 . A method of alleviating or treating a lung defect in a mammal, said method comprising administering to said mammal a therapeutically effective amount of a composition comprising a three dimensional construct capable of supporting and maintaining the differentiation state of an lung cell, thereby alleviating or treating said lung defect in said mammal. 
     
     
         35 . An implantable composition comprising a decellularized tissue capable of supporting cell growth, wherein the decellularized tissue exhibits a characteristic of a corresponding natural tissue prior to decellularization. 
     
     
         36 . The composition of  claim 35  comprising a population of cells, wherein said composition is capable of supporting and maintaining the differentiation state of a lung cell. 
     
     
         37 . The composition of  claim 36 , wherein said population comprises a stein cell. 
     
     
         38 . The composition of  claim 36 , wherein said population comprises epithelial and endothelial cells. 
     
     
         39 . The composition of  claim 36 , wherein said cells are genetically modified.