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Researchers develop 3D-printed human liver tissue for drug screening

Engineers and researchers at the University of California San Diego developed a 3D-printed liver tissue model that is similar to the human liver, indicated for use for patient-specific drug screening and disease modeling, according to published findings in Proceedings of the National Academy of Sciences.

“It typically takes about 12 years and $1.8 billion to produce one FDA-approved drug,” Shaochen Chen, PhD, director of the Biomaterials and Tissue Engineering Center at UC San Diego, said in a press release. “We've made a tool that pharmaceutical companies could use to do pilot studies on their new drugs, and they won't have to wait until animal or human trials to test a drug's safety and efficacy on patients. This would let them focus on the most promising drug candidates earlier on in the process.”

Shaochen Chen

Chen and colleagues, including Shu Chien, PhD, director of the Institute of Engineering in Medicine at UC San Diego, used bioprinting technology to produce 3D microstructures that mimic biological tissues. This technology, also developed in Chen’s laboratory, assisted in printing the human-like liver tissue in two steps. First, the tissue was printed in a honeycomb pattern of 900 small hexagons that were derived from human induced pluripotent stem cells (hiPSCs). Next, endothelial and mesenchymal cells were printed in the spaces between the hexagons, according to the research.

Shu Chien

These cells are important because they are patient-specific, which makes them “ideal materials for building patient-specific drug screening platforms,” according to the release. In addition to this, extracting any cells from the liver to build liver tissue will not be needed because the cells came from a specific patient’s skin cells.

“We’ve engineered a functioning liver tissue that matches what you’d see under a microscope, Chen said in the release.

After harvesting the model in vitro for at least 20 days, the tissue’s ability to perform liver functions was tested. Liver functions included albumin secretion and urea production and results were then compared with other models.

Compared with a 2D monolayer culture and 3D hepatic progenitor cells (HPC)-only model, this 3D model showed improved morphological organization, enhanced liver-specific gene expression levels, increased metabolic product secretion and enhanced cytochrome P450 induction over weeks of in vitro culturing.

The researchers concluded: “The hepatic model developed in this study provides a 3D environment for hiPSC-derived hepatic cells in triculture with supporting cells in a hepatic lobule microarchitecture and has the ability to facilitate in vitro maturation and functional maintenance of hiPSC-derived hepatic cells in a biomimetic microenvironment.”

Disclosure: The researchers report no relevant financial disclosures.