Burcin Ekser, MD, PhD, recently earned a grant to support groundbreaking research in the development of advanced 3-D bioprinted human liver models. A transplant surgeon and director of the IU School of Medicine Xenotransplantation Lab, Ekser received the 2019 American Society of Transplant Surgeons (ASTS) Foundation Faculty Development Grant, awarded to only one researcher each year. Ekser was singled out by the ASTS for his work to create the models using scaffold-free 3D bioprinting technology available through the Indiana Clinical and Translational Sciences Institute. The $100,000 grant will help fund Ekser’s scientific research through 2021.
The ASTS-supported research focuses on human liver model bioprinting, which offers valuable near-term benefits for drug toxicity testing and lays important groundwork for the eventual creation of lifesaving human whole-liver bioprints for transplantation. The research program builds on Ekser’s pioneering efforts to bioprint pig liver tissue from genetically engineered pig liver cells.
With the funding, Ekser’s team, which includes fellow IU School of Medicine researchers Lester Smith, PhD, and Ping Li, PhD, will attempt to print mini human liver models with four-and five-cell line combinations, which would be the most advanced human liver models ever made. The team will also explore methods for extending the models’ survival, aiming to surpass the 28-day lifespan of a three cell-line model, the longest cited in published literature. Ekser said the team hopes to extend model survival to at least a month, and ideally two months, to provide for ample drug toxicity testing.
“Often, the liver toxicity of medications isn’t revealed immediately, so developing the capability to test them for longer periods of time is critical to ensure the drugs don’t become dangerous to human life,” Ekser explained. “Current drug testing only isolates one liver cell, typically hepatocytes, in 2D in vitro cultures, where testing is limited to just one to two days because the hepatocytes lose their functionality in the culture environment.”
3D bioprinting is a significant step forward with scaffold free being the most advantageous type of bioprinting because models are made without biological materials that could potentially interact with the cells. The result is bioprinted models that more closely resemble true physiological conditions, making them even more viable for a variety of studies.
“If we can 3D bioprint models of different liver diseases, such as fatty liver, primary biliary cholangitis or primary sclerosing cholangitis—conditions that can destroy the human liver, we will have a tool to understand what is the marker or gene that triggers these diseases, and we can study potential drugs to treat them,” Ekser said. “If we can use this technology to overcome different liver diseases, transplants may be needed for fewer people in the future.”
For those who do need liver transplants, Ekser is hopeful further research and technological advancements will make 3D bioprinting of full-size human livers for transplantation a reality in 20 or more years. With concurrent developments in stem cell research, he predicts scientists will be able to print a liver for transplant using the patient’s own stem cells, eliminating the need for anti-rejection medications.
“The technology is advancing very fast, and I am grateful to the ASTS and other funding agencies because without their help, we cannot explore, we cannot advance in this important research,” Ekser said.