Vitro epithelial models comprising lamina propria-derived cells

Abstract

An in vitro microfluidic “organ-on-chip” is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic “organ-on-chip”, e.g. “epithelia-on-chip” further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic “organ-on-chips” allow identification of cells and cellular derived factors driving disease states in addition to drug testing for reducing inflammation effecting epithelial regions.

1 - 121 . (canceled) 
     
     
         122 . A microfluidic device comprising:
 a) a membrane positioned between a bottom surface of a chamber and a microchannel; and   b) at least one epithelial cell type, at least one stromal cell type, and a gel disposed in said first chamber, said gel positioned between the membrane and said at least one epithelial cell type.   
     
     
         123 . The microfluidic device of  claim 122 , wherein said epithelial cell type is selected from the group consisting of epithelial cells of the lung, epithelial cells of the skin and epithelial cells of the urogenital tract. 
     
     
         124 . The microfluidic device of  claim 122 , wherein said epithelial cells of the lung are selected from the group consisting of alveolar epithelial cells and airway epithelial cells. 
     
     
         125 . The microfluidic device of  claim 122 , wherein said at least one stromal cell type is disposed within said gel. 
     
     
         126 . The microfluidic device of  claim 122 , wherein said at least one stromal cell type is disposed between said gel and said membrane. 
     
     
         127 . The microfluidic device of  claim 122 , wherein said at least one stromal cell type is disposed between said gel and said at least one epithelial cell type. 
     
     
         128 . The microfluidic device of  claim 122 , wherein said at least one stromal cell type is a lamina propria-derived cell. 
     
     
         129 . The microfluidic device of  claim 122 , wherein said device has a removable top covering said chamber. 
     
     
         130 . A method comprising:
 a) providing a microfluidic device comprising i) a membrane positioned between a bottom surface of a chamber and a microchannel, and ii) at least one epithelial cell type, at least one stromal cell type, and a gel disposed in said first chamber, said gel positioned between the membrane and said at least one epithelial cell type; and   b) perfusing said microfluidic device with fluid.   
     
     
         131 . The method of  claim 130 , wherein said epithelial cell type is selected from the group consisting of epithelial cells of the lung, epithelial cells of the skin and epithelial cells of the urogenital tract. 
     
     
         132 . The method of  claim 130 , wherein said epithelial cells of the lung are selected from the group consisting of alveolar epithelial cells and airway epithelial cells. 
     
     
         133 . The method of  claim 130 , wherein said at least one stromal cell type is disposed within said gel. 
     
     
         134 . The method of  claim 130 , wherein said at least one stromal cell type is disposed between said gel and said membrane. 
     
     
         135 . The method of  claim 130 , wherein said at least one stromal cell type is disposed between said gel and said at least one epithelial cell type. 
     
     
         136 . The method of  claim 130 , wherein said at least one stromal cell type is a lamina propria-derived cell. 
     
     
         137 . The method of  claim 130 , wherein said device has a removable top covering said chamber. 
     
     
         138 . The method of  claim 137 , further comprising the step of c) removing said removable top. 
     
     
         139 . The method of  claim 138 , further comprising the step of d) introducing an agent into said chamber.