3D InSight™ Human Liver Microtissues

3D InSight™ Human Liver Microtissues are prequalified, long-lived liver models designed for drug safety and efficacy testing, and the study of healthy and diseased liver function. Composed of the primary human liver cells necessary for core liver functions, these microtissues are delivered assay-ready, in a lab-automation-friendly plate format ideal for screening.

Pre-validated and standardized, 3D InSight™ Human Liver Microtissues have been thoroughly characterized on a functional, transcriptomic, and proteomic level. This model represents a functional and physiologically relevant in vitro liver model that maintains stable function for more than 5 weeks in culture and is therefore well suited for a broad range of liver research applications, such as DILI (drug induced liver injury) prediction.

InSight™ Human Liver Microtissues offer the most biologically- relevant, standardized, and scalable solution in the marketplace with proven performance and quality.

Classical 2D cell cultures have various limitations, as cultures are short lived (up to 3-5 days) not allowing long-term compound exposures and hepatocytes lose their organ specific characteristics due to un-physiological conditions. In contrast, 3D cultures are long lived (4 weeks and longer) and cells maintain organ-specific characteristics throughout the entire culturing time.

3D InSight™ Human Liver Microtissues are produced using scaffold-free cellular self-assembly of primary human hepatocytes and non-parenchymal liver cell types, such as Kupffer cells, and liver endothelial cells, to recapitulate native-tissue-live functionality. Because they are viable for up to four weeks in culture, they are ideal for studies that require short and long-term compound exposure. They exhibit albumin secretion, polarized hepatocyte cellular organization, robust cytochrome P450 activity, high mitochondrial function, and bile-acid transport to bile canaliculi.

Representing the smallest functional unit of liver tissue, these microtissues have in vivo-like morphology and physiology that reflects human liver biology. Morphological characterization of 7-day old human liver microtissues. A.H&E staining shows overall cytoarchitecture, periodic acid-Schiff (PAS) staining identifies glycogen incorporation, and immunohistochemistry for CD68 demonstrates the presence of Kupffer cells. Positive staining for bile-salt export pump (BSEP, apical marker) and multidrug resistance protein 2 (MRP2, apical marker) reveals a highly polarized cell organization. B. Viability of human liver microtissues was monitored over 5 weeks of culture time for changes in microtissue diameter, ATP content, and albumin secretion. Microtissues showed high stability, with no significant loss of microtissue size over time. Microtissue viability, as determined by ATP content, was also stable over time. The albumin secretion was very stable over 28 days of culture time, but dropped from day 28 to 35. This suggests that the intrinsic functional lifetime of hepatocytes in this culture system is limited to 4–5 weeks in culture. (Messner et al., 2017)

3D Solution Benefits

3D spheroid models bridge the gap from 2D in vitro models to the clinic providing more clinically relevant results.

A joint study (Proctor et al., 2017) conducted by collaborators at AstraZeneca and Genentech, resulted in a systematic validation of InSphero’s 3D InSightTM Human Liver Microtissues versus 2D primary human hepatocytes using a panel of 110 clinically known drugs. InSightTM Human Liver Microtissues showed a 2-fold higher sensitivity (61%) in identifying known hepatotoxicants compared to conventional 2D liver models.

The scalability of InSphero microtissues and easy handling of the AkuraTM plate technology allow for cost efficient processing and handling of 3D microtissues.