TBUSA supports liver toxicology and drug discovery with best-in-class tools and services
The Society of Toxicology works to improve health and safety globally by increasing the impact of toxicology. The annual SoT conference was held in Baltimore, MD, on March 12–16, 2017, providing opportunities for attendees to share their research and expertise.
Adding to the body of expertise at SoT 2017, Takara Bio USA, Inc. offered attendees guidance, technologies, and services for advancing their drug discovery and drug metabolism studies. Our predictive in vitro models demonstrate unparalleled consistency and functionality, enabling extended toxicity and safety pharmacology studies. For example, our Cellartis human induced pluripotent stem (hiPS) cell-derived hepatocytes are functional for up to three weeks post-thawing, and thus are more suitable for long-term testing than any other hepatic cell model on the market.
Check out the poster we presented and our featured products and services, below.
Poster presentation at SoT 2017
Human pluripotent stem cell-derived hepatocytes with extended culture time provide a robust and efficient platform for long term toxicology studies
Human pluripotent stem (hPS) cell-derived hepatocytes have the potential to serve as predictive human in vitro model systems for drug discovery, drug metabolism research, and hepatotoxicity studies, provided they possess relevant hepatocyte functions. Importantly, some hepatocyte applications, like chronic toxicity testing, demand a 2-week usage window, an order of magnitude outside standard culturing practices.
Here, we show data for a newly developed maintenance medium allowing culturing of the hPS cell-derived functional hepatocytes for 14 days, and thus enables their use for new applications with longer culture times. We have performed multiple analyses, including RT-qPCR, immunostainings, and functional assays, to investigate if our hepatocyte differentiation and maintenance system will 1) generate mature hepatocytes from multiple hPS cell lines, and then 2) to support their functionality during an extended culture time. Importantly, the hPSC-derived hepatocytes expressed important genes of the drug metabolizing machinery, such as CYPs, phase II enzymes and transporters during the entire culture time. Interestingly, the hepatocytes generated from different hPS cell lines show diverse CYP expression profiles, reflecting the inter-individual variation present in the human population.
Next, we exposed these novel hPS cell-derived hepatocytes to known hepatotoxins for up to 14 days and found they respond correctly to these toxic compounds with an increasing sensitivity upon longer exposure, demonstrating their utility for chronic toxicology studies. Taken together, our hepatocyte differentiation system along with the new maintenance medium can reliably generate and maintain hPS cell-derived hepatocytes from different genetic backgrounds.
Since we observed that our new maintenance medium substantially extended the life-span of hPS cell-derived hepatocytes, we tested if it also could extend the life-span of human primary hepatocytes. Interestingly, we found that cryopreserved human primary hepatocytes cultured in the new maintenance medium were viable and showed stable activities of several key CYP enzymes for several weeks in conventional 2D cultures, sharply contrasting existing hepatocyte maintenance medias. Thus, it seems that our novel maintenance medium prevents the de-differentiation of primary hepatocytes that usually occurs as an adaptation to 2D culture systems. The novel maintenance medium enables the use of human primary hepatocytes in conventional 2D cultures for applications requiring longer culture times without the need to culture in complicated and less user-friendly 3D systems.
Featured products and services at SoT 2017
Create >90% pure hiPS cell-derived hepatocytes with diverse genetic backgrounds
The Cellartis iPS Cell to Hepatocyte Differentiation System provides a complete solution for generating functional, hiPS cell-derived hepatocytes within three weeks. As an alternative to using primary hepatocytes for toxicology and pharmacology studies, these hepatocytes exhibit sufficient expression levels of drug-metabolizing enzymes and transporters and demonstrate stable functionality over time in culture. Derived from your own patient- or disease-specific hiPS cell lines, these cells can provide an accurate reflection of the metabolic diversity observed in the human population.
Ready-made hepatocytes derived from hiPS cells
Cellartis Enhanced hiPS-HEP cells are a highly homogeneous population of hepatocytes derived from hiPS cells. These hepatocytes express metabolic enzymes relevant to hepatotoxicity, making them ideal for in vitro drug discovery, drug metabolism, pharmacology, and toxicology studies.
Expertise to assist any stage of your toxicology research
With Cellartis Human Pluripotent Stem Cell Services, you can focus on your areas of expertise and leave the challenges to us. Our 15+ years' experience with endodermal lineage differentiation means you can count on us to deliver high-quality, functional hepatocytes and cardiomyocytes specifically tailored to your needs.
Ready-made cardiomyocytes derived from hiPS cells
Cellartis cardiomyocytes are a highly homogeneous population of cardiomyocytes derived from hiPS cells. The cardiomyocytes are suitable for use in safety pharmacology and cardiotoxicity testing and on multiple high-throughput platforms.