image: FRESH 3D bioprinted perfusable liver tissue inside of a bioreactor.
Credit: Carnegie Mellon College of Engineering
A Carnegie Mellon University-led team has secured an award of up to $28.5 million from the Advanced Research Projects Agency for Health (ARPA-H) to develop a functional, 3D bioprinted liver for patients with acute liver failure. The project, called LIVE, or Liver Immunocompetent Volumetric Engineering, aims to provide a temporary liver that supports regeneration of a patient’s own liver, reducing the need for full organ transplants. The project is under ARPA-H’s Personalized Regenerative Immunocompetent Nanotechnology Tissue (PRINT) program, which is led by ARPA-H Program Manager Ryan Spitler, Ph.D.
LIVE addresses a major public health challenge. Each year in the United States, about 100,000 organ transplants are performed, while another 100,000 people remain on transplant waiting lists. Millions more would benefit from organ replacement but do not qualify for a transplant.
“The goal is to create a piece of liver tissue that you can use as an alternative to transplant, specifically for acute liver failure,” said Adam Feinberg, professor of biomedical engineering at Carnegie Mellon and principal investigator. “The liver we are creating would last for about two to four weeks. It would give patients time for their own liver to regenerate, and then, they would not need a liver transplant, freeing up those livers for other patients. The liver is just the first application, with the plan to expand to the heart, pancreas, and other organs. This innovation would fundamentally change healthcare as we know it, because most people suffer at some point from end-stage organ failure.”
The team is co-lead by Kelly Stevens, a professor of bioengineering at the University of Washington, together with experts in liver stem cells, biomanufacturing, biomaterials, hepatology, transplantation, pre-clinical models, and regenerative medicine from Charité – Universitätsmedizin Berlin, FluidForm Bio, Inc., Iowa State University, Mayo Clinic, the University of Pittsburgh, and the University of Washington. The project will use Carnegie Mellon’s FRESH 3D bioprinting and 3D ice platforms to create biologic livers composed entirely of human cells and structural proteins, such as collagen. The livers are engineered to be immune compatible, eliminating the need for immune suppression medications, which are often toxic and damaging to patients’ liver and kidney function.
“The challenge is really the immune system,” Feinberg elaborated. “We are going to be using hypoimmune cells, which are engineered to be universal donor, so anyone can have the cells and tissues we are building without needing to take immune suppression.”
Within five years, the team hopes to have the bioengineered liver working at adult-scale and ready for pre-clinical testing prior to the first human clinical trials.
LIVE is part of a broader effort to address organ shortages and advance bioengineered solutions for life-threatening conditions. Beyond acute liver failure, the technologies developed through the ARPA-H PRINT program could be adapted to other liver conditions and even other organs, including the heart and kidney.
“The LIVE project is going to significantly advance organ biofabrication for transplant by funding our highly capable team that combines the very best engineers, biologists, and clinicians,” Feinberg added. “The technologies and capabilities we develop will also have impact beyond the liver, enabling additional efforts to build human tissue and organs to treat congenital heart defects, heart disease, blindness, and Type I diabetes.”
This publication was supported by the Advanced Research Projects Agency for Health (ARPA-H) under Award Number D25AC00460-00, providing up to $28,520,065 for a 60-month period. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Advanced Research Projects Agency for Health.