by • February 7, 2016 • No Comments
A team led by engineers at the University of California, San Diego has 3D-printed a tissue that closely mimics the human liver’s sophisticated structure and function. The new version may be utilized for patient-specific drug screening and disease versioning. The work was published the week of Feb. 8 in the online early version of Proceedings of the National Academy of Sciences.
Researchers said the advance may assist pharmaceutical companies save time and money when developing new drugs.
“It typically takes of 12 years and $1.8 billion to create one FDA-approved drug,” said Shaochen Chen, NanoEngineering professor at the UC San Diego Jacobs School of Engineering. “That’s for the reason over 90 percent of drugs don’t pass animal tests or human clinical trials. We’ve created a tool that pharmaceutical companies may 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 may let them focus on the most promising drug candidates earlier on in the process.”
Chen and Shu Chien, a professor of Medicine and Bioengineering, director of the Institute of Engineering in Medicine at UC San Diego and recipient of a National Medal of Science, are co-senior authors of the study.
The liver plays a significant role in how the body metabolizes drugs and creates key proteins. This is why liver versions are increasingly being created in the lab as platforms for drug screening. But, existing versions so far lack both the harsh micro-architecture and diverse cell makeup of a real liver.
The UC San Diego team engineered a human liver tissue version that additional closely looks like the real thing—a diverse combination of liver cells and supporting cells processatically organized in a hexagonal pattern.
“We’ve engineered a functioning liver tissue that matches what you’d see under a microscope,” said Chen.
“The liver is one-of-a-kind in that it receives a dual blood donate with different types of pressures and chemical constituents. Our version has the future of reproducing this intricate blood donate process, thus providing unprecedented belief of the harsh coupling between circulation and metabolic functions of the liver in health and disease,” said Chien, who studies how blood flow and pressure affect blood vessels.
To do this, the team employed a novel bioprinting innovation created in Chen’s lab, that can quickly create harsh 3D microstructures that mimic the sophisticated showcases discovered in biological tissues. The liver tissue was printed in two steps. First, the team printed a honeycomb pattern of 900-micrometer-sized hexagons, every containing liver cells derived of human induced pluripotent stem cells. An advantage of human induced pluripotent stem cells is they are patient-specific, that makes them perfect materials for assembling patient-specific drug screening platforms. And since these cells are derived of a patient’s skin cells, researchers don’t require to extract any cells of the liver to create liver tissue.
In the following step, endothelial and mesenchymal supporting cells were printed in the spaces between the stem-cell-containing hexagons.
The entire structure—a 3 × 3 millimeter square, 200 micrometers thick—takes only seconds to print. This is a vast improvement over other methods to print liver versions, that typically take hours.
The structure was cultured in vitro for at very least 20 days. The researchers and so tested the resulting tissue’s skill to perform different types of liver functions, such as albumin secretion and urea production, and compared it to other versions. They discovered that their version was able-bodied to maintain these functions over a longer time period than other liver versions. Their version in addition expressed a relatively higher level of a key enzyme that is considered to be involved in metabolizing most of the drugs administered to patients.
“I ponder that this can assist as a excellent drug screening tool for pharmaceutical companies and that our 3D bioprinting innovation opens the door for patient-specific organ printing in the future,” said Chen.
“The liver tissue created by this novel 3D printing innovation can in addition be incredibly useful in reproducing in vitro disease versions such as hepatitis, cirrhosis, and cancer,” introduced Chien. “Such realistic versions can be invaluable-bodied for the study of the pathophysiology and metabolic abnormalities in these diseases and the efficacy of drug therapies.”
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