In vitro epithelial models comprising lamina propria-derived cells

Patent metadata

Field	Value
Publication number	US-11833512-B2
Application number	US-202117215900-A
Country	US
Kind code	B2
Filing date	Mar 29, 2021
Priority date	Dec 2, 2016
Publication date	Dec 5, 2023
Grant date	Dec 5, 2023

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.

First claim

What is claimed is:

1. A microfluidic device comprising:
a) a first microfluidic channel in fluidic communication with a second microfluidic channel, with a semi-permeable membrane disposed between said first and second microfluidic channels; and
b) at least one epithelial cell type, at least one stromal cell type, and a gel disposed in said first channel, said gel positioned between the membrane and said at least one epithelial cell type.

2. The microfluidic device of claim 1 , 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.

3. The microfluidic device of claim 2 , wherein said epithelial cells of the lung are selected from the group consisting of alveolar epithelial cells and airway epithelial cells.

4. The microfluidic device of claim 1 , wherein said at least one stromal cell type is disposed within said gel.

5. The microfluidic device of claim 1 , wherein said at least one stromal cell type is disposed between said gel and said membrane.

6. The microfluidic device of claim 1 , wherein said at least one stromal cell type is disposed between said gel and said at least one epithelial cell type.

7. The microfluidic device of claim 1 , wherein said at least one stromal cell type is a lamina propria-derived cell.

8. A method comprising:
a. providing a microfluidic device comprising i) a first microfluidic channel in fluidic communication with a second microfluidic channel, with a semi-permeable membrane disposed between said first and second microfluidic channels, ii) at least one epithelial cell type, at least one stromal cell type, and a gel disposed in said first channel, said gel positioned between the membrane and said at least one epithelial cell type; and
b. perfusing said microfluidic device with fluid.

9. The method of claim 8 , 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.

10. The method of claim 9 , wherein said epithelial cells of the lung are selected from the group consisting of alveolar epithelial cells and airway epithelial cells.

11. The method of claim 8 , wherein said at least one stromal cell type is disposed within said gel.

12. The method of claim 8 , wherein said at least one stromal cell type is disposed between said gel and said membrane.

13. The method of claim 8 , wherein said at least one stromal cell type is disposed between said gel and said at least one epithelial cell type.

14. The method of claim 8 , wherein said at least one stromal cell type is a lamina propria-derived cell.

Assignees

• Emulate Inc

Inventors

• Kerns S Jordan
• Barrile Riccardo
• Hamilton Geraldine
• Karalis Catherine
• Levner Daniel
• Lucchesi Carolina
• Varone Antonio
• Villenave Remi

Classifications

• B01L3/502753 Primary

  characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation · CPC title

• B01L3/502715

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• C12M23/16 Primary

  Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title

• C12M29/04

  Filters; Permeable or porous membranes or plates, e.g. dialysis · CPC title

• C12M35/08

  Chemical, biochemical or biological means, e.g. plasma jet, co-culture · CPC title