BME’s Chris Chen leads a team at the Wyss Institute to combine tissue engineering with synthetic biology, laying the foundation for “smart” solid organ therapies.
By Benjamin Boettner, Wyss Institute
In patients developing end-stage liver disease, the damage has become too severe for the liver’s normally extraordinary regenerative capacity to repair or compensate for it. Once this “point of no return” has been reached, the only option is an organ transplant. However, getting a liver transplant is extremely difficult due to high demand and limited supply – about 9,000 to 10,000 people with liver disease are on the U.S. national transplant list at any given time, and roughly 20% of them become too sick to receive a transplant or die while waiting.
Ambitious efforts are on the way that eventually could enable the engineering of entire implantable liver organs. But thus far, the maximum size of laboratory-engineered liver constructs remains limited and cannot provide therapeutic benefits for patients yet. Now, a research team at the Wyss Institute at Harvard University, Boston University, and MIT led by Wyss Institute Core Faculty member Christopher Chen, M.D., Ph.D. and Associate Faculty member Sangeeta Bhatia, M.D., Ph.D., have approached this important problem from a different angle. Their findings are published in Science Advances.
“We asked if it would be possible to first implant a small-scale liver construct and then drive it to expand in the body following its engraftment. A sufficiently grown, functional ‘satellite liver’ could immediately relieve the metabolic burden in a damaged liver and help bridge the time until a transplant becomes available,” said Chen. “This project was a natural extension of our longtime collaboration in engineering liver tissue therapeutics, and a perfect combination of Sangeeta’s expertise in nanotechnologies and liver bioengineering, and mine in cellular engineering and vascularizaton.” Chen is also the William Fairfield Warren Distinguished Professor of Biomedical Engineering and Director of the Biological Design Center at Boston University. He also is a leader of the Wyss Institute’s 3D Organ Engineering Initiative, and team lead of the recently awarded ARPA-H PRINT-supported ImPLANT project, which focuses on whole organ liver engineering at the Wyss and collaborating institutions.
Researchers developed BOOST (Bioengineered On-demand Outgrowth via Synthetic Biology Triggering), a new strategy in which small engineered tissues are implanted first and then grown on demand inside the body. By rewiring gene expression in primary liver hepatocytes and fibroblasts, the team was able to effectively switch on a tissue growth program in an implanted liver graft, circumventing the challenges of growing a large tissue in a dish.