Liver organoid model for pharmacoinetic assay

Original method for generating a liver organoid with hepatobiliary connection

Advantages

  • Scalable in vitro model for drug development
  • Induction and long-term maintenance of CYP3A4 activity and Albumin secretion
  • Monitoring available for metabolism or hepatotoxicity of potential drugs in vitro
  • Possible for reconstituting functional hepatobiliary tissue

Background and Technology

Large number of healthy hepatocytes for hepatotoxicity testing in vitro can be isolated from a single rat or from a human liver resection or autopsy. However, primary hepatocytes reduce their function in culture, are limited to obtain, and have lot variation.  To avoid these issues, many in vitro drug safety tests have been conducted using established human hepatoma cell lines such as HepG2 and HepaRG or stem cells derived from liver.  But so far, few approaches have succeeded in reproducing a liver organoid with hepatobiliary function.  Inventors have succeeded in efficient hepatobiliary organoid from rat/mouse small hepatocyte (SH※) and mouse biliary epithelial cell (BEC) and established it by the following protocol.  It remains high reproductivity at the level of connection site between hepatocyte and bile duct. Furthermore, the inventors have been progressing in demonstration with human hepatocytes or those derived from human stem cells.
※Original SH preparing method has been established via inventors previous research

<Protocol>
1.  Type I collagen solution will be treated and turned into a gel
2.  EpCAM(+) BEC cells will be seeded and cultured till the concentration reaches to a certain level
3.  SH cells will be added to the BEC and be cultured
4.  Type I collagen containing Matrigel will be deposited layers again

Data

  • Connection site by bile canaliculi was formed between hepatocyte and bile duct.
  • Fluorescein Diacetate was taken in hepatocyte, metabolized and came into the bile duct.  The inventor also demonstrated Bilirubin uptaken by hepatocytes was accumulated in bile ducts.
    Liver Organoid

 

 

Patent

Pending ; not published yet

Researcher

Dr. Naoki Tanimizu, et al. (Sapporo Medical University, Japan)

Expectations

We are looking for a CRO or a pharmaceutical company to develop and use this hepatocyte model for in vitro hepatotoxicity testing.

Product No. : CD-03088

 

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