An academic team co-cultured HepG2 and hepatic stellate LX-2 cells to form a liver tumor spheroid model. Spheroids with a collagen-rich outer layer showed reduced doxorubicin penetration; disrupting that layer improved the drug response in the model.
Researchers at the University of Twente and collaborating medical centers used a soft-embossed microwell array to co-culture HepG2 hepatocellular carcinoma (HCC) cells with LX-2 hepatic stellate cells in different proportions. They cleared the resulting spheroids for imaging and stained for type I collagen to examine how cellular composition shaped the extracellular matrix (ECM).
Some compositions developed an extracellular-matrix-rich capsule around the spheroid. That feature matters to drug testing because the amount of drug reaching tumor cells may depend on the surrounding matrix, as well as on the cells’ intrinsic sensitivity.
The combined presence of hepatic stellate cells and extracellular matrix hindered doxorubicin penetration and reduced its therapeutic effect in vitro. Enzymatic degradation of the matrix-rich capsule improved penetration and the observed drug effect.
A four-platform comparison combined lipid imaging, liver-function measurements, expression profiling and CYP assays. Lipid accumulation did not uniformly reduce drug metabolism, and differences depended on the model and donor.
A 512-compound screen in patient-derived motor neurons identified resveratrol tetramers with neuroprotective activity. Follow-up work covered 14 iPSC lines and linked protection to changes in neuronal excitability.
