New Method Supports Sustained Perfusion of Transplanted Bioengineered Livers

By Will Boggs MD

October 19, 2019

NEW YORK (Reuters Health) - A new optimized method for revascularizing bioengineered livers provides up to 15 days of continuous perfusion after transplantation into immunosuppressed pigs.

"In our research, we discovered (that) human umbilical-vein endothelial cells (HUVECs), a cell type that can be easily sourced and banked for manufacturing, can not only revascularize the liver grafts to enable long-term vascular flow; they can also demonstrate an ability to become similar to the native liver endothelial cells, called sinusoidal endothelial cells, which are critical to native liver function," said Dr. Jeffrey J. Ross from Miromatrix Medical Inc., in Eden Prairie, Minnesota.

"This finding reinforces the importance of the decellularized matrix in directing cellular function and overall specificity. It also provides an easier path to a final clinical product utilizing a HUVEC source," he told Reuters Health by email.

In earlier studies, implanted bioengineered livers have not exceeded three days of continuous perfusion. Dr. Ross and colleagues developed an optimized method for revascularizing a porcine liver scaffold using HUVECs as a primary cell source.

These cells localized within sinusoidal regions and, over time, appeared to transition towards a liver sinusoidal endothelial cell-like phenotype.

The team achieved up to 15 days of continuous perfusion of these revascularized bioengineered livers following heterotopic implantation in pigs under a steroid-based immunosuppression protocol, they report in Nature Biomedical Engineering, online October 14.

Following graft implantation, the recipient-animal immune response included the development of HUVEC-reactive antibodies and complement activation, which appear to be the likely drivers of eventual graft rejection and thrombosis.

"The current research is targeted for the clinic, which is why it is taking place on human-size liver grafts," Dr. Ross said. "Having solved the critical vascular issue, we are now able to include hepatocytes and bile duct cells within the liver grafts to bioengineer the whole liver. These grafts are being implanted into pigs, and the results are very encouraging. We've had preliminary talks with the U.S. Food and Drug Administration (FDA) and defined required steps before this research can be tested in human clinical trials."

Co-author Dr. Scott L. Nyberg of Mayo Clinic, in Rochester, Minnesota, told Reuters Health by emsil, "The only efficacious treatment for medically refractory liver failure is a liver transplant. However, there is an acute shortage of donor livers, and many patients die waiting for a transplant. This discovery gives hope that solutions to the organ shortage are on the horizon."

Miromatrix, a privately funded company, owns the patent rights for the perfusion decellularization and recellularization technologies used in the study. Five of the 21 authors of this report were employed by Miromatrix which, along with a Mayo Clinic Innovation grant, funded this research.


Nat Biomed Eng 2019.