The technique has the potential to one day create a working liver for transplantation into people with severe liver disease, or be used as an interim measure for a patient who must wait until a conventional donor organ becomes available.
The study, “Decellularized liver matrix as a carrier for transplantation of human fetal and primary hepatocytes in mice,” has been accepted by the journal Liver Transplantation and is now online.
The innovative technique devised by the UC Davis scientists working in Sacramento, Calif., involved “decellularizing” a mouse liver – stripping all cells out of the organ while preserving its protein structure and blood supply framework. Using the decellularized liver as a scaffold, the researchers inserted human liver cells into the structure, prompting the cells to survive longer and function better in this native liver scaffold. The scaffold with liver cells was then implanted into the fatty tissue of a mouse abdomen, where it functioned well for two months after transplantation. Researchers say that having the cells function for at least 60 days is an important milestone in the research work now under way to create new organs and tissues from stem cells.
“We have demonstrated the best results to date for the efficacy of transplanting cells into an animal model using a decellularized liver matrix,” said Jian Wu, an adjunct professor of internal medicine and senior author of the study. “This is an important step in the pathway to providing people suffering from liver failure with more hope and a much better chance of survival.”
New approaches to treating liver failure are critically needed, according to Mark Zern, a senior member of the research team, professor of internal medicine and director of the UC Davis Transplant Research Program. “There are not enough organs available for transplant, and many patients die waiting for one,” said Zern.
About 25,000 people are on waiting lists around the country for liver transplants, but only 6,000 to 7,000 organs become available each year. The liver is essential for life and has many complex functions: It stores glucose, as well as many vitamins and minerals; makes blood-clotting factors and the building blocks of proteins; and detoxifies impurities that enter the bloodstream.
The method of decellularizing an organ and transplanting new working cells into animals using this scaffold has been used experimentally in research to regenerate other organs such as the heart, trachea, lungs and kidneys. Until now, other studies to create a functioning liver have been rudimentary and have only resulted in hours or days of activity rather than months.
Ping Zhou, the first author of the study, along with Wu and their UC Davis colleagues, are continuing their research, with a focus on regenerating livers that will function well over an extended period.
“We are very excited about the clinical applications of this research,” said Jan A. Nolta, another senior member of the research team and a professor of cell biology and human anatomy, as well as the director of the UC Davis stem cell program and its Institute for Regenerative Cures. “Our ultimate goal is to ‘scale it up’ to help humans in the future.”
Other authors of the study are Nataly Lessa, Daniel C. Estrada, Ella B. Severson and Shilpa Lingala, all from the UC Davis stem cell or transplant research programs.
The study was supported by grants from the National Institutes of Health, the California Institute for Regenerative Medicine, as well as UC Davis Stem Cell Program start-up funding and the UC Davis Technology Transfer Fund.
UC Davis is playing a leading role in regenerative medicine, with nearly 150 scientists working on a variety of stem cell-related research projects at campus locations in both Davis and Sacramento. The UC Davis Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine (CIRM), opened in 2010 on the Sacramento campus. This $62 million facility is the university’s hub for stem cell science. It includes Northern California’s largest academic Good Manufacturing Practice laboratory, with state-of-the-art equipment and manufacturing rooms for cellular and gene therapies. UC Davis also has a Translational Human Embryonic Stem Cell Shared Research Facility in Davis and a collaborative partnership with the Institute for Pediatric Regenerative Medicine at Shriners Hospital for Children Northern California. All of the programs and facilities complement the university’s Clinical and Translational Science Center, and focus on turning stem cells into cures. For more information, visit www.ucdmc.ucdavis.edu/stemcellresearch.