Nature Scientific Reports Article Touts Versatility, Promise of 3D Human Liver Microtissues for Drug Development
Schlieren, Switzerland, June 16, 2016 – Liver spheroids display longer culture lifetime, liver-like functionality, and increased sensitivity for detection of hepatotoxic drugs.
Research published by the Karolinska Institute and collaborators as part of the European Community Innovative Medicine Initiative project (MIP-DILI) offers further, independent verification of the utility and promise of 3D liver microtissues for studying liver function, liver diseases, and long-term drug-induced liver injury (DILI). The research was published last month in Nature Scientific Reports, an open-access journal.
The paper demonstrates the extended in vitro lifetime and organotypic characteristics of primary human hepatocytes (PHH) when cultured in a scaffold-free 3D configuration, displaying viability and liver-like functionality for up to five weeks in culture. Proteomic analysis revealed that inter-individual variability was retained between spheroids generated from different individual hepatocyte donors. The study also used the prolonged in vitro lifespan of 3D cultured hepatocytes to perform chronic exposure testing of known DILI-inducing drugs and found they could predict toxicity at clinically relevant doses. In addition, the spheroid model system proved to be suitable for studying liver diseases such as cholestasis and steatosis.
Commenting on the publication, Dr. Jens M. Kelm, Chief Scientific Officer and co-founder of InSphero AG, says the paper “Reinforces to the scientific community the benefits of 3D liver microtissues for the purpose of safety assessment during drug development. 3D liver models show enhanced culture lifetime in comparison to standard 2D cultured hepatocytes. This allows for long-term, repeat dose exposure studies and enhances the sensitivity and predictive power of the model.”
InSphero uses its patent-pending 3D Select™ Process to enable industrial-scale production of 3D liver microtissues for in vitro liver research and DILI testing conducted by the world’s largest pharmaceutical and chemical companies. Dr. Kelm notes that InSphero has performed similar proteomic and genomic characterization of its 3D InSight™ Human Liver Microtissues grown over 28 days in culture, results presented at the EuroTox Annual Meeting in 2015.
InSphero’s 3D Select™ Process yields liver microtissues with consistent morphology and viability by ensuring only the healthiest cells are incorporated into tissues, a critical difference from conventional methods. “Cryopreserved hepatocytes contain large numbers of necrotic and functionally compromised cells. This percentage varies greatly between donor lots and vendors, making it challenging to make uniform microtissues in the numbers needed for industrial-scale testing. Through our 3D Select™ Process, we remove these compromised cells prior to the aggregation step, making microtissue formation more reliable while improving morphology and viability. This translates to a more robust, mechanistically accurate in vitro model that enables testing standardization across multiple sites and across the industry as a whole.”
