3D InSight™ Human Liver Microtissues

Insphero offers advanced 3D in vitro technology for immuno-oncology screening, and presents the 3D InSight™ Tumor Microtissue in the assessment of Antibody-Drug Conjugates (ADCs) efficacy and penetration depth. InSphero further highlights the product's capabilities including the evaluation of various therapeutic modalities, such as antibody-based therapeutics, with confidence, covering mechanisms of action, immune cell engagement, off-target effects, and more.

Tumor spheroids are three-dimensional cellular models that mimic the complex microenvironment of tumors, facilitating advanced drug screening and research in oncology. InSphero introduces 3D InSight™ Tumor Spheroids for advanced immuno-oncology (IO) drug discovery. The spheroids offer high physiological relevance, scalability, and reliability, effectively modeling the complex tumor microenvironment (TME). With a wide array of tumor cell lines, including cancer-associated fibroblasts (CAFs) and immune cells, these spheroids mimic tumor heterogeneity and microenvironment interactions.

3D tumor spheroids comprise of various tumor cell lines and components of the tumor microenvironment, therefore accurate testing of anti-cancer therapies while maintaining consistency and reproducibility can prove challenging. InSphero highlights human 3D InSight™ Tumor Spheroids, offering a blend of physiological relevance, scalability, and reliability for oncology therapeutic testing. With the flexibility to accommodate different throughput needs and the capability to mimic tumor heterogeneity, they provide a robust platform for advanced drug discovery in oncology.

Cancer ranks as the second leading cause of death globally, with immunotherapy offering promise but facing limitations in clinical success. Recent studies reveal that overexpression of PU.1, IRF8, and BATF3 transcription factors induces the transformation of tumor cells into antigen-presenting dendritic cells, potentially enhancing anticancer immunity. However, existing testing platforms struggle to replicate the intricate cell interactions necessary to validate this approach. InSphero presents the 3D InSight™ Oncology Platform as a tool to assess the efficacy and immune-stimulatory effects of tumor-dendritic cell reprogramming.

In this application note, explore the InSphero MASH CALL initiative, a fast and cost-effective identification of drug candidates in MASH (Metabolic Dysfunction-associated Steatohepatitis, renamed from NASH). Furthermore, discover how the 3D InSight™ Liver Microtissue MASH model is a robust, reproducible and translational model that can recapitulate human hallmarks of MASH predictive of clinical candidates.

This technical note details a protocol for determining injury to liver hepatocytes as measured through the release of alpha-GST. Hepatocytes contain high amounts of metabolic enzymes, which are released upon cellular injury into the cell culture supernatant. Beside the commonly used markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alpha GST (αGST) is increasingly being used as a liver injury marker. αGST provides advantages as a biomarker for hepatotoxicity due to its high cytosolic concentration in hepatocytes and its rapid release upon their injury. Detection of alpha-GST release is therefore a specific and early indicator of hepatocyte injury.

This application note details a protocol to isolate total RNA from as little as 1 microtissue (~ 1000 cells) using the ReliaPrep™ RNA Tissue Miniprep System. Isolation of high quality total RNA from cultured cells is important for various analyses in cell-based drug discovery and toxicity. Analytical applications such as quantitative real time PCR or microarray analysis depend on robust RNA isolation procedures.

This application note demonstrates the analysis of ATP in 3D microtissues using the CellTiterGlo® 3D Cell Viability Assay and 3D InSight™ Microtissues in GravityTrap™.

Isolation of high quality total RNA from cultured cells is important for various analyses in cell-based drug discovery and toxicology. Analytical applications such as quantitative real time PCR or microarray analysis depend on robust RNA isolation procedures. This application note describes a protocol to isolate total RNA from as little as 1 3D InSight™ Human Liver microtissue (approx. 1000 cells) using a commercially available, semi-automated RNA extraction robot from Promega.

Drug-induced liver injury remains the main cause of liver failure and post-market drug withdrawals. In this poster long-term three-dimensional co-cultured human liver microtissues were characterized to assess their suitability for use in drug-induced hepatotoxicity studies.

In this video, learn how Insphero’s 3D InSight™ Human Liver Microtissues are morphologically and functionally superior 3D models with a long lifetime; supplied ready-to-use with validated 3D assay protocols.

3D InSight Human Liver Disease platform provides the most physiologically relevant testing environment for efficacy and safety

3D human liver microtissues comprised of pooled hepatocytes from multiple donors offers more genetically diverse model for DILI detection and prediction