Fetal Pulmonary Cells and Uses Thereof

Abstract

Isolated mixed populations of fetal pulmonary cells, engineered three-dimensional tissue constructs of these cells, and uses thereof in identifying therapeutic agents which augment, repair, and/or replace dysfunctional native lung and to perform in vitro studies such as pharmaceutical screening, models for lung development and disease and characterization of chemical or mechanical injury are provided.

1 .- 8 . (canceled) 
     
     
         9 . A method for assessing pharmaceutical activity and/or toxicity of an agent in pulmonary tissue comprising:
 contacting an engineered three-dimensional pulmonary tissue construct with the agent, wherein the engineered construct comprises:
 a population of fetal pulmonary cells comprising epithelial, endothelial, and mesenchymal cells; 
 a three-dimensional matrix of natural polymers comprising collagen or elastin; and 
 a combination of fibroblast growth factors (FGF); and 
   assessing an effect of the agent on the engineered three-dimensional pulmonary tissue construct.   
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 9 , wherein the matrix is permissive to cell-cell and cell-growth factor interactions. 
     
     
         12 . The method of  claim 9 , wherein the matrix comprises a hydrogel or a mixture of a synthetic polymer and collagen or elastin. 
     
     
         13 . The method of  claim 9 , wherein the combination of FGF comprises at least FGF10, FGF7, and FGF2. 
     
     
         14 . The method of  claim 9 , wherein the step of assessing the effect of the agent comprises measuring cell viability and proliferation. 
     
     
         15 . The method of  claim 9 , wherein the population further comprises mast cells. 
     
     
         16 . The method of  claim 15 , wherein the step of assessing the effect of the agent comprises examining inflammatory processes. 
     
     
         17 . The method of  claim 9 , wherein the effect of the agent comprises inducing epithelial or endothelial morphogenesis. 
     
     
         18 . The method of  claim 9 , wherein the step of assessing the effect of the agent comprises measuring epithelial structures. 
     
     
         19 . The method of  claim 18 , wherein the epithelial structures comprise alveolar forming units. 
     
     
         20 . The method of  claim 9 , wherein the step of assessing the effect of the agent comprises measuring formation of endothelial networks. 
     
     
         21 . The method of  claim 20 , wherein the endothelial networks comprise capillary tubes. 
     
     
         22 . The method of  claim 9 , wherein the step of assessing the effect of the agent comprises measuring secretion of growth factors.