Integrated human organ-on-chip microphysiological systems

Patent metadata

Field	Value
Publication number	US-11773359-B2
Application number	US-202117146264-A
Country	US
Kind code	B2
Filing date	Jan 11, 2021
Priority date	Dec 9, 2011
Publication date	Oct 3, 2023
Grant date	Oct 3, 2023

Abstract

The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

First claim

What is claimed is:

1. A device, comprising hepatocytes on a first side of a membrane, and microvascular endothelial cells on a second side of said membrane, with Kupffer cells positioned under said endothelial cells.

2. The device of claim 1 , wherein said hepatocytes are human hepatocytes.

3. The device of claim 2 , wherein said hepatocytes are patient-specific hepatocytes isolated from tissue.

4. The device of claim 1 , wherein said membrane is an ECM-coated membrane.

5. The device of claim 4 , wherein said ECM-coated membrane is coated with laminin.

6. The device of claim 4 , wherein said ECM-coated membrane is coated with type IV collagen.

7. The device of claim 1 , wherein said microvascular endothelial cells are human endothelial cells.

8. A method, comprising:
a) providing hepatocytes on a first side of a membrane in a first channel, and microvascular endothelial cells on a second side of said membrane in a second channel, with Kupffer cells positioned under said endothelial cells; and
b) culturing said cells.

9. The method of claim 8 , wherein said hepatocytes are human hepatocytes.

10. The method of claim 8 , wherein said hepatocytes are patient-specific hepatocytes isolated from tissue.

11. The method of claim 8 , wherein said membrane is an ECM-coated membrane.

12. The method of claim 11 , wherein said ECM-coated membrane is coated with laminin.

13. The method of claim 11 , wherein said ECM-coated membrane is coated with type IV collagen.

14. The method of claim 8 , wherein said microvascular endothelial cells are human endothelial cells.

15. A method, comprising:
a) providing hepatocytes on a first side of a membrane in a first channel, and microvascular endothelial cells on a second side of said membrane in a second channel, with Kupffer cells positioned under said endothelial cells; and
b) introducing an agent such that it comes in contact with said hepatocytes.

16. The method of claim 15 , wherein said agent is a drug.

17. The method of claim 16 , further comprising c) assessing toxicity of said drug.

18. The method of claim 16 , further comprising c) assessing clearance of said drug.

19. The method of claim 16 , further comprising c) assessing pharmacokinetics of said drug.

20. The method of claim 15 , wherein said hepatocytes are exposed to said agent by flowing a fluid containing the agent through said first channel.

Assignees

• Harvard College

Inventors

• Ingber Donald E
• Bahinski Anthony
• Cunningham Robert
• Goss Josue A
• Hamilton Geraldine A
• Hinojosa Christopher David
• Levner Daniel
• Parker Kevin Kit

Classifications

• C12M23/58

  Reaction vessels connected in series or in parallel (combinations of bioreactors with other apparatus, C12M43/00) · CPC title

• A01N1/148

  with provisions specially adapted for transporting · CPC title

• A01N1/143

  for organ perfusion · CPC title

• A01N1/122

  Preservation or perfusion media · CPC title

• A01N1/10

  Preservation of living parts · CPC title