3-D Technology May Improve Development of Drugs for Liver Disease

Discovery holds promise for treatment of cirrhosis and liver damage related to hepatitis C.

A new 3D printed tissue model that closely mimics human liver function and structure can save money and time for developing new drugs, a recent study indicates.

"It typically takes about 12 years and $1.8 billion to produce one FDA-approved drug," said co-senior author Shaochen Chen. "That's because over 90% of drugs don't pass animal tests or human clinical trials. 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."

The study was published in the Proceedings of the National Academy of Sciences and performed at UC San Diego. The researchers engineered the model with a diverse combination of liver cells, as well as supporting cells systematically organized in a hexagonal pattern that mimicked what is seen under a microscope.

"The liver is unique in that it receives a dual blood supply with different pressures and chemical constituents,” said co-senior author of study Shu Chien. “Our model has the potential of reproducing this intricate blood supply system, thus providing unprecedented understanding of the complex coupling between circulation and metabolic functions of the liver in health and disease."

Currently, there is an increase in the development of liver models for drug screenings. This is because the liver plays a critical part in how the body metabolizes drugs and produces proteins.

Unfortunately, previous models lacked the ability to closely mimic a liver.

During the study, researchers used novel bioprinting technology that produces complex 3D microstructures that mimic biological liver tissues. This was done rapidly and printed in 2 steps.

The first step was to print a 900 micrometer sized hexagon — resembling a honeycomb pattern – that contained liver cells that came from human induced pluripotent stem cells, which are patient specific. Since the cells come from the patient’s skin cells, they don’t need to take cells from the liver in order to build the liver tissue.

The second step involved printing endothelial and mesenchymal supporting cells in the spaces that are between the hexagons.

This new printed model takes mere seconds to print, which is a significant improvement from other methods that could take hours.

The structure was 3 by 3 millimeters squared and 200 micrometers thick, and was cultured in vitro for a minimum of 20 days. Next, the resulting tissue’s ability to perform liver functions, like albumin secretion and urea production, were tested and compared against other models.

The results of the study showed that compared with other models, the new model was able to maintain functions for a longer period of time. The model was also able to express a relatively higher level of key enzyme, which is involved in metabolizing drugs in patients.

"I think that this will serve as a great drug screening tool for pharmaceutical companies and that our 3D bioprinting technology opens the door for patient-specific organ printing in the future," Chen said.

"The liver tissue constructed by this novel 3D printing technology will also be extremely useful in reproducing in vitro disease models such as hepatitis, cirrhosis, and cancer," Chien added. "Such realistic models will be invaluable for the study of the pathophysiology and metabolic abnormalities in these diseases and the efficacy of drug therapies."