We've updated our Privacy Policy to make it clearer how we use your personal data. We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement

3D Liver Spheroid Model in Use by MIP-DILI

Listen with
Speechify
0:00
Register for free to listen to this article
Thank you. Listen to this article using the player above.

Want to listen to this article for FREE?

Complete the form below to unlock access to ALL audio articles.

Read time: 1 minute

Leaders of the European project "Mechanism based Integrated systems for the Prediction of Drug Induced Liver Injury" (MIP-DILI) project have reported they will use 3-dimensional (3D) liver spheroids against a panel of other in vitro test systems aimed at developing novel preclinical tests to improve the safety evaluation of drugs likely to cause drug-induced liver toxicity before subsequent evaluation in clinical trials.  Along with its academic and EFPIA partners, the MIP-DILI consortium is funded equally by the EU Innovative Medicines Initiative (IMI) and EFPIA companies, and is in year three of the €32.4 million 5-year program.

In early project work, primary human hepatocytes (PHH), cells isolated from human liver donors, outperformed tumor-derived or other immortalized liver cell lines in terms of metabolic activity but with apparently mixed sensitivity to known DILI-inducing drugs.  InSphero, the leading supplier of 3D cell culture products and services to the pharmaceutical industry, along with a number of other commercial technology suppliers were invited to participate in the next round of studies, where PHH were grown and assayed in a variety of formats that included static 2D culture, perfusion cultures, and 3D spheroids. Among the participating commercial suppliers contributing to the study, 3D spheroids emerged as the culture platform that most resembled liver-like biology and responded to a number of liver toxins with a certain enhanced sensitivity, which now requires further investigation.

Dr. Phil Hewitt, co-leader of the project's 'Established and novel in vitro cell systems' work package, says "3D spheroids proved to offer more than just superior biological relevance, they also provide the scalability and compatibility necessary to work with commercial assays and automation systems, and can do it at a more reasonable cost than other systems evaluated in the early phase studies.  Liver spheroids will play a key role in the predictive in vitro tests being developed as the project progresses."

The findings were presented last fall at EUROTOX 2014 in Edinburgh, UK, in talks that summarized a thorough two-year evaluation of available liver cell sources and cell culture formats being considered.