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.

1 - 39 . (canceled) 
     
     
         40 . A method for 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. 
     
     
         41 . The method of  claim 40 , wherein said decellularized scaffold exhibits an intact airway tree and vascular network. 
     
     
         42 . The method of  claim 40 , wherein said population comprises a stem cell. 
     
     
         43 . The method of  claim 40 , wherein said population comprises epithelial and endothelial cells. 
     
     
         44 . The method of  claim 40 , wherein said cells are genetically modified. 
     
     
         45 . The method of  claim 40 , wherein said decellularized scaffold is capable of supporting and maintaining the differentiation state of an alveolar epithelial cell. 
     
     
         46 . The method of  claim 40 , wherein said scaffold comprises a biocompatible 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. 
     
     
         47 . The method of  claim 40 , comprising cells that exhibit gene expression associated with induction of branching morphogenesis. 
     
     
         48 . The method of  claim 40 , wherein said gene is cystic fibrosis transmembrane conductance regulator (CFTR). 
     
     
         49 . The method of  claim 40 , 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. 
     
     
         50 . 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. 
     
     
         51 . The method of  claim 50 , wherein said engineered three dimensional tissue is derived from a decellularized scaffold. 
     
     
         52 . The method of  claim 50 , wherein the test agent is selected from the group consisting of a chemical agent, a pharmaceutical, a peptide, a nucleic acid, and radiation. 
     
     
         53 . The method of  claim 50 , wherein the test agent is a delivery vehicle for a therapeutic agent. 
     
     
         54 . The method of  claim 50  comprising determining the effect of the test agent on cell number, area, volume, shape, morphology, marker expression or chromosomal fragmentation. 
     
     
         55 . The method of  claim 50 , further comprising the step of selecting an agent which has a desired effect on the lung tissue model. 
     
     
         56 - 58 . (canceled) 
     
     
         59 . 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.