Nearly 25,000 people were on the U.S. liver transplant waiting list in 2020, but because recipients and donors must have compatible biological makeups to ensure the body accepts the donation, only about 38% of those waiting received an organ. Transplantation remains the only cure for many patients with end-stage liver disease, but this shortage of donor organs makes it inaccessible for thousands. Now, a research project that includes an engineer from Penn State, funded as part of Phase I of the Genesis Mission initiative, seeks to discover a solution to this critical problem.
The Terasaki Institute for Biomedical Innovation (TIBI) in California has been awarded a contract worth up to $19.8 million to lead a multi-institution effort to use bioprinting - a process that layers the fundamental building blocks of organ tissue to build a larger structure - to engineer transplantable, immune-compatible liver tissue. Xiaojun "Lance" Lian, associate professor of biomedical engineering and of biology at Penn State, will contribute to the project through his work mitigating the immune response a recipient's body might have to the printed organ and help establish biological acceptance.
"Through the project, we hope to engineer an organ that will be a similar size to a real human liver," Lian said. "This will be the first time that researchers aim to make a human organ that can be used for transplantation without immune system rejections."
The initiative, titled "Prometheus," takes its name from the Greek Titan whose liver was said to regenerate daily, a myth long tied to the organ's regenerative capacity. Funded under the Advanced Research Projects Agency for Health (ARPA-H) PRINT program, the project centers on engineering a universal, immune-compatible liver cell source. Using cost-effective, scalable culture methods and bioprinting, the team intends to assemble those cells into functional, transplantable liver tissue.
Xiling Shen, principal investigator on the project and acting director of TIBI, said the project is aimed at easing donor scarcity and the lifelong immunosuppression that transplant patients require today.
"This award allows us to bring together bioengineering, stem cell biology and transplant medicine to build a liver that doesn't require a donor match," Shen said. "It's a step toward making organ replacement scalable rather than scarce."
According to Lian, the interdisciplinary nature of the project will help the team approach this major challenge of printing organ tissue from various angles. Using a Penn State-licensed and patented technology developed in Lian's lab, the team will provide a pathway to efficiently obtain the needed quantities of specialized stem cells - which can be coaxed into different cell types as needed - the project's livers require. The technology specifically enables the team to engineer commercially sourced stem cells into hypoimmune stem cells that help suppress immune system responses without traditional immunosuppressant treatments that can leave a person vulnerable to infection.
"A major challenge in developing off-the-shelf engineered tissues is creating a cell source that can evade immune rejection across different patients," Lian said. "Using hypoimmune stem cells for differentiation, the process where general stem cells transform into more specialized agents, we will remove the need to worry about immune rejection from the engineered liver."
Once the team builds the tissue, they will also test how it functions. If successful, Lian said, the project could establish a scalable, donor-independent path to liver replacement, easing a shortage that currently leaves thousands of patients without options and reducing the lifelong burden of immunosuppression for those who do receive a transplant.
In addition to multidisciplinary experts from TIBI, the project team also includes researchers from the University of California, Los Angeles, Washington University in St. Louis, Israel Institute of Technology, Rice University and industry partners Technion and Pluristyx.
This research was funded, in part, by ARPA-H. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the U.S. Government.
